Scientific Stuff
This Discussion Forum is for discussion of scientific stuff that doesn't directly relate to patient care.
Please review and follow our usual ground rules, at Ground Rules. For example, anything smacking of advertising by a sales rep will be deleted without warning. (To share your thoughts, use the "Comments" link immediately below. Instructions for entering comments may be found at How to Enter Comments. I have also posted some discussion of Etiquette for Commenting.)
Bill the diabetesdoc
info@diabetesmonitor.com
Diabetes.Blog.Com is a blogcompanion to our main website, the Diabetes Monitor, which you can find at http://www.diabetesmonitor.com
Using 40 grams of Pumpernickel bread and 2 units of Novolog I found a peak rise of 60 mg/dL. After 5 hours my BG was 10 mg/dL higher than when I started.
Using the same amount of Pumpernickel bread and Novolog, I added 57 grams of cheese containing 20 g of fat and 12 g of protein . . . no carbs. This time the peak rise was only 45 mg/dL. After 5 hours my BG was 20 mg/dL lower than when I started.
The bottom line for me is that the same amount of insulin had greater effect when protein and fat was added to the meal. This result greatly complicates optimum insulin dosing. But if it can be understood then a new insulin dosing strategy can be devised. (Comment this)
JM "Since I could not find obtain the isomer I started looking at foods that had higher concentrations of it. You have Inositol, which has a lot of inositol isomers inclusive of d-Chiro-Inositol, lecithin has 2-6% of d- Chiro-Inositol, and US patent number 6699511 from a pinitol-containing carob extract, which looks to be 10 to 11% pinitol. Pinitol is (3-O-methyl-D-chiro-inositol, which behaves similarly to D-Chiro-Inositol."
The tables in the article cited below have quite a bit of information on the substances you have mentioned. Others from the same department at Cornell University have published information on substances in buckwheat.
myo-Inositol, D-chiro-Inositol, and D-Pinitol Synthesis, Transport, and Galactoside Formation in Soybean Explants -
http://crop.scijournals.org/cgi/content/full/45/4/1312
Since losing 40 pounds of 195, insulin resistance is not my primary problem. I'm early on the learning curve for this topic that concerns the pyrovate dehydrogenase (PDH) complex - http://web.indstate.edu/thcme/mwking/tca-cycle.html.
"The reactions of the PDH complex serves to interconnect the metabolic pathways of glycolysis, gluconeogenesis and fatty acid synthesis to the TCA cycle." Type 2 diabetics are generally deficient in d-Chiro-Inositol and it impacts insulin resistance. Circulating factors and insulin resistance. I. A novel myoinositol 1,2- cyclic phosphate phosphoglycan insulin antagonist from human plasma is elevated in noninsulin-dependent diabetes mellitus - http://jcem.endojournals.org/cgi/content/abstract/80/8/2419
"cyclic phosphate. This IPG epitope inhibits insulin-stimulated rat adipocyte (fat cell) glucose oxidation and lipogenesis by a noncompetitive mechanism."
Frank (Comment this)
Protein stimulates insulin secretion, but it also stimulates glucagon secretion, and it's supposed to be the ratio of the two that is important. People with type 2 have too much glucagon and too little insuln.
How does the protein effect work in a type 2? (Comment this)
Enhancing the Action of Incretin Hormones: A New
Whey Forward? -
http://www.glucagon.com/ENDOWheyDruckerJuly2006.pdf
A scholar.google.com search for leucine+amino+acids diabetes+glucose+regulation+BCAA+trials+human -
http://tinyurl.com/2y2uxd
There are some clues in these links. (Comment this)
"How does the protein effect work in a type 2?"
The effect might vary dependent on waist circumference as well as the state of ones insulin secretion.
"We conclude that, across the range of 0–30 g, protein and fat reduced glycemic responses independently from each other in a linear, dose-dependent fashion, with protein having ~3-times the effect of fat. A large protein effect was associated with high WC and high dietary-fiber intake, whereas a large fat effect was associated with low FPI (fasting plasma insulin). These conclusions may not apply to solid meals."
The Effects of Fat and Protein on Glycemic Responses in Nondiabetic Humans Vary with Waist Circumference, Fasting Plasma Insulin, and Dietary Fiber Intake -
http://jn.nutrition.org/cgi/content/abstract/136/10/2506 (Comment this)
DPP4_GINGIVALIS is a protein similar in action and structure to DPP-4. DPP-4 cleaves GLP-1 and shortens the active time in our bodies to approximately 90 seconds. GLP-1 has shown great benefits in the treatment of type-2 diabetes. So is there a relationship between periodontal disease Gingivitis and type-2 diabetes.
I theorize that the Gingivitis bacteria are a parasite that excretes DPP-4 like chemicals, which cause higher blood sugars in the blood. Then the gums bleed and/or the bacteria feed on the additional sugars and nutrients.
There is speculation as to whether or not DPP-4 inhibitors like Januvia, Galvus and Saxagliptin interfere with the immune t-cell function. The identification of yeasts, bacteria, fungus and Gingivitis that produce DPP-4 like chemicals leads me to believe that DPP-4 can and is artificially inflated by many common oral parasites. So administering small amounts of DPP-4 inhibitors may actually bring the DPP-4 into normal ranges.
These parasitical additions to DPP-4 like proteins in the body may explain some hyperactive t-cell production above the norm. Because of this speculation I’m less worried about DPP-4 inhibitors reducing the immune response below normal. I think we may find that these DPP-4 mimics increase t-cell responses above normal. These increases in t-cell response are hyperactive in a type 2 diabetic, like gum swelling. Since Gingivitis is anaerobic so even the swelling response my improve the environment in the mouth to the bacteria by allowing less oxygen to get to the gums.
There is some discussion whether pre-diabetic patients should be put on drugs that inhibit DPP-4s. In instances where the patient also has significant Gingivitis there may be two reasons to prescribe.
http://www.biochemj.org/bj/373/0179/bj3730179f03.htm?resolution=HIGH
http://www.biochemj.org/bj/311/0835/3110835.pdf
http://www.biochemj.org/bj/imps_x/pdf/BJ20021914.pdf
(Comment this)
I'm curious about the mechanism of this, but they say in the Abstract that they need more studies to decide this. (Comment this)
The abstract that I previously cited concerned "The Effects of Fat and Protein on Glycemic Responses in Nondiabetic Humans" so I am attempting to isolate the topic to type 2 diabetics. I put quite a few terms into the search string but still ended up with a lot of finds. My initial search had 34 thousand finds.
A scholar.google.com search for "amino acids"+ proteins+food+insulin+secretion+"type 2"+diabetes resulted in 2.9 thousand finds -
http://tinyurl.com/2x6x7y. Note that Acrp30 is another name for adiponection which is a substance secreted from fat cells. A higher level is supposed to reduce insulin resistance. The first article listed has 699 articles citing it. Adding "resistance" to the above search string still gives 2,500 finds. If you note the number of articles citing the first ten finds, you can see that this is a hot topic for researchers. Adiponectin secreted from visceral fat goes right to the liver by means of the portal vein. Inflammation is also reduced by weight loss of related to visceral fat (the fat under the abdominal muscles). I don't think this was the answer you were looking for, but try printing out some of the articles for more insight. (Comment this)
Thanks but I don't have time to peruse that many articles at the moment. It was Derek who brought this topic up. What I was hoping for was an explanation by someone who had already done the research and could summarize it for others <G>. (Comment this)
To me these short handles are needed as the beginning for understanding. So Acrp30 is similar to DPP-4 and GLP-1. We can talk about it and do internet research on the subject far more easily. Once I memorize the short handle then the next step is to flesh it out for myself in simple terms.
(Comment this)
I remember more easily with nicknames or trade names like Byetta than with names such as AJ567fg. Or "the 'Blubber' symphony" instead of "symphony No 4567 in F flat."
So too, "adiponectin," which says something about its action, is easier to remember than ACRP30. Same with ghrelin and obestatin. They jog the memory. (Comment this)
I like adiponectin rather than ACRP30 because it points back to the adipose (fat) tissues that are it's source. Adiponectin comes in more than one form. While adiponectin has been credited for lower insulin resistance and inflammation, when I inquired about it my doctor had never heard of it and the local lab did not have a test for it's levels. (Comment this)
There are instances where I prefer acronyms to the full descriptors when it comes to memorization. I don't take a absolute stand on any of the terms. I like AMPK where the K stands for kinase since I don't always remember all of the other abbreviations. (Comment this)
The scientists from various international institutions believe their findings explain up to 70 per cent of the genetic background of Type II diabetes – a diseases that affects over 1.9m people in the UK and is characterised by either low levels of, or an inadequate response to insulin - a hormone secreted by the pancreas to release energy from the breakdown of carbohydrates......
www.drugresearcher.com/news/ng.asp?n=74124-diabetes-type-imperial-college-london-genetic-test-illumina
Just a coment from me I have felt for so long it was all my fault even thought I know better.
There are so many people who do not know anything about Diabetes THINK it is all the persons fault that they have it and make comments about how you brought it on yourself.
(Comment this)
Great post. SLC30A8 a Zinc Transporter in Vesicles of Beta-Cells is one of these genetic issues identified in 70% of Type 2 diabetics. This is exciting, because it gives a genetic test for diabetes and an inference that there is interference with Zinc transport in the beta-cells. This makes me wonder whether Zinc supplementation can help. There is no indication that ingesting Zinc in excess of RDA of 15mg can increase the deficient Zinc transport, but I’m willing to give it a try. Careful reading will lead you to the conclusion that daily intake of 150mg or more is a very bad idea leading to Copper deficiency. High amounts of Zinc are toxic. It looks like 25mg is reasonable while 50mg should raise concerns of Copper deficiency.
Some of the research indicates that key diabetic features are helped by Zinc.
Zinc may improve serum cholesterol levels in hemodialysis patients. There is some evidence that zinc may improve cholesterol ratio of HDL "good cholesterol" versus LDL "bad cholesterol" which would be considered a positive effect.
Diabetic patients typically have significantly lower serum zinc levels compared with healthy controls. Based on one randomized, controlled trial, zinc supplementation for type-2 diabetics may have beneficial effects in elevating their serum zinc level, and in improving their glycemic control that is shown by decreasing their HbA1c% concentration.
Oral zinc supplementation may improve glycemic control and severity of peripheral neuropathy
Deficiency symptoms include wound-healing, wasting of body tissues, cognitive function, and hormonal function.
So it looks like a promising supplement. This is just the major genetic factor traced from this research.
(Comment this)
There's a recent publication (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17253560&query_hl=1&itool=pubmed_docsum) suggesting that it doesn't help prevent diabetes. Doesn't mean it wouldn't hurt once you have it.
I'm always a little suspicious of studies that say "diabetics" have this and that if they don't differentiate between types 1 and 2, well controlled, poorly controlled, etc.
People with poorly controlled diabetes lose a lot of things in their urine along with the excess glucose. (Comment this)
You said, "There is speculation as to whether or not DPP-4 inhibitors like Januvia, Galvus and Saxagliptin interfere with the immune t-cell function. The identification of yeasts, bacteria, fungus and Gingivitis that produce DPP-4 like chemicals leads me to believe that DPP-4 can and is artificially inflated by many common oral parasites. So administering small amounts of DPP-4 inhibitors may actually bring the DPP-4 into normal ranges."
Your hypothesis, at least on the surface, would seem to have some validity worth testing. Galvus and Saxagliptin inhibit DPP-8 & -9 less than Januvia. Do you know what the pharmacological doses of inhibition are for DPP-8 & -9? (Comment this)
www.diabetes-symposium.org/index.php?menu=view&id=322
(Comment this)
Someone else caught your post here and started a thread on the misc.health.diabetes and alt.support.diabetes newsgroups. It continued on for about 2 weeks.
Frank (Comment this)
Current approaches in the treatment of type 2 diabetes focus on alleviating the target tissue deficiencies. Treatments can reduce hepatic glucose production, increase peripheral insulin sensitivity, or enhance insulin secretion. Most patients with type 2 diabetes require some combination of treatments, and ultimately might need to include insulin as part of their regimen. Exendin-4 is a glucagon-like peptide-1 (GLP-1) homolog and an agonist for the GLP-1 receptor. It lowers the blood glucose levels through a distinct mechanism complementary to the mechanisms of action of currently available anti-diabetic drugs. By decreasing glucagon and increasing insulin secretion in a glucose-dependent manner, Exendin-4 may stimulate β-cell proliferation, restore β-cell sensitivity to glucose, delay gastric emptying, and increase peripheral sensitivity to glucose. Despite these effects, the clinical application of Exendin-4 is limited by its relatively short half-life in plasma (<1 hour). CJC-1134-PC, the modified Exendin-4 analogue conjugated to recombinant human albumin, is based on ConjuChem's PC-DACTM technology. This preformed conjugate, besides having a much longer half-life than its natural counterpart is only slightly less potent. Based on the combined preclinical data, ConjuChem has moved forward with the development of CJC-1134-PC for the treatment of type 2 diabetes. Data from a phase I/II single escalating dose clinical study demonstrated an excellent tolerability profile and positive efficacy on glucose reduction supporting once-a-week dosing. The product is a highly soluble small volume liquid formulation injected subcutaneously utilizing a very small gauge (29 to 31) needle.
http://conjuchem.hyphenhealth.com/science/AboutPCDAC.shtml
(Comment this)
Thank you for the link I am hoping that my Endo will give me a loaner Continues monitor so I can find out what effects my blood sugars. (Comment this)
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia, Charlottesville, VA, USA. zandong_yang@merck.com
Type 1 diabetes mellitus (T1DM) is an autoimmune disease leading to near complete pancreatic beta-cell destruction. New evidence suggests that beta-cell regeneration is possible, but ongoing autoimmune damage prevents restoration of beta-cell mass. We tested the hypothesis that simultaneously blocking autoimmune cytokine damage and supplying a growth-promoting stimulus for beta-cells would provide a novel approach to reverse T1DM. Therefore, in this study we combined lisofylline to suppress autoimmunity and exendin-4 to enhance beta-cell proliferation for treating autoimmune-mediated diabetes in the non-obese diabetic (NOD) mouse model. We found that this combined therapy effectively reversed new-onset diabetes within a week of therapy, and even maintained euglycemia up to 145 days after treatment withdrawal. The therapeutic effect of this regimen was associated with improved beta-cell metabolism and insulin secretion, while reducing beta-cell apoptosis. It is possible that such combined therapy could become a new strategy to defeat T1DM in humans.
Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16643856&dopt=Abstract (Comment this)
The company is also in early development stages with Amylin Pharmaceuticals (AMLN) to develop a nasal spray formulation of the diabetes drug Byetta, which cannot be given by mouth and requires multiple daily injections.
http://www.fool.com/investing/general/2007/05/16/nastech-nose-potential.aspx
(Comment this)
This helped me understand more about Byetta and how it works
http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=3996 (Comment this)
(1) Please spend some time at the Diabetes Monitor website (CLICK HERE) and read more about diabetes.
(2) Be sure to tell your family, friends, support group, diabetes nurse educator, and your doctor about this website!
(3) Read the disclaimer about Google ads (on the right-side sidebar on every page).
(4) Also: if you haven't yet answered our polls to tell us more about yourself, we'd encourage you to please do so:
(5) Finally, if you like to answer polls, there are lots more at the Diabetes Monitor, at Polls.
Recently a company called VeraLight developed a spectroscopic tool that diagnoses diabetes and pre-diabetes just by measuring the fluorescence reflected by AGEs in your skin. VeraLight expects to launch its product, which gives results in only sixty seconds, late this year.
The portable desktop device, called "Scout," weighs about ten pounds and resembles a drugstore blood pressure monitor. When you place the palm side of your forearm on to the machine, it shines various wavelengths of light onto your skin. The light excites electrons in the collagen-linked AGEs, causing them to emit light of a lower energy that is then measured by the machine.
In recent studies, VeraLight's Scout significantly outperformed two common diagnostic blood tests, the fasting plasma glucose (FPG) test and the A1c test, in identifying diabetes and pre-diabetes in people with one or more known risk factors for the disease. A prototype of the device was able to identify 29% more patients than the FPG test and 17% more patients than the A1c test.
Source: VeraLight
Diabetes Care, May 2007
http://www.diabeteshealth.com/read/2007/06/17/5240.html#comments
http://www.veralight.com/ (Comment this)
Finding flourescent pigments increasing corelates to Type 2 Diabetes. This seems to link lipofuscin, ceroid, and age pigment-like fluorophores with Type 2 Diabetes. So this verilight sounds like a great tool.
But the real issue is whether or not these flourescent pigments can be removed from the body. Durk Pearson & Sandy Shaw have been looking at that for years. Will reducing these pigments improve blood sugar control?
(Comment this)
Antihyperglycemic activity of Tarralin, an ethanolic extract of Artemisia dracunculus L.
Ribnicky, D. M.; Poulev, A.; Watford, M.; Cefalu, W. T.; Raskin, I.
Biotech Center, Cook College, Rutgers University, New Brunswick, NJ, USA.
Phytomedicine (2006), 13(8), 550-557.
Publisher: Elsevier GmbH, CODEN: PYTOEY ISSN: 0944-7113. Journal written in English. AN 2006:1169418 CAPLUS
Abstract
The studies reported here were undertaken to examine the antihyperglycemic activity of an ethanolic ext. of Artemisia dracunculus L., called Tarralin in diabetic and non-diabetic animals. In genetically diabetic KK-A.gamma. mice, Tarralin treatment by gavage (500 mg/kg body wt./day for 7 days) lowered elevated blood glucose levels by 24% from 479 25 to 352 16 mg/dL relative to control animals. In comparison, treatment with the known antidiabetic drugs, troglitazone (30 mg/kg body wt./day) and metformin (300 mg/kg body wt./day), decreased blood glucose concns. by 28% and 41%, resp. Blood insulin concns. were reduced in the KK-A.gamma. mice by 33% with Tarralin, 48% with troglitazone and 52% with metformin. In (STZ)-induced diabetic mice, Tarralin treatment, (500 mg/kg body wt./day for 7 days), also significantly lowered blood glucose concns., by 20%, from 429 41 to 376 58 mg/dL relative to control. As a possible mechanism, Tarralin was shown to significantly decrease phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression by 28% in STZ-induced diabetic rats. In non-diabetic animals, treatment with Tarralin did not significantly alter PEPCK expression, blood glucose or insulin concns. The ext. was also shown to increase the binding of glucagon-like peptide (GLP-1) to its receptor in vitro. These results indicate that Tarralin has antihyperglycemic activity and a potential role in the management of diabetic states.
(Comment this)
Ribnicky, David M.; Poulev, Alexander; O'Neal, Joseph; Wnorowski, Gary; Malek, Dolores E.; Jager, Ralf; Raskin, Ilya.
Cook College, Biotech Center, Rutgers University, New Brunswick, NJ, USA.
Food and Chemical Toxicology (2004), 42(4), 585-598.
Publisher: Elsevier Science B.V., CODEN: FCTOD7 ISSN: 0278-6915. Journal written in English. CAN 141:53265 AN 2004:170949 CAPLUS
Abstract
TARRALIN is an ethanolic ext. of A. dracunculus (Russian tarragon), a common medicinal and culinary herb with centuries of use. A. dracunculus is a close relative of the French or cooking tarragon and contains components common to many herbs that are routinely consumed without reported adverse effects. Since safety information of A. dracunculus and its ext. is limited to historical use, TARRALIN was examd. in a series of toxicol. studies. Complete Ames anal. did not reveal any mutagenic activity either with or without metabolic activation. TARRALIN was tested in an acute limit test at 5000 mg/kg with no signs of toxicity noted. In a 14 day repeated dose oral toxicity study, rats appeared to well tolerate 1000 mg/kg/day. Subsequently, TARRALIN was tested in an oral subchronic 90-day toxicity study (rat) at doses of 10, 100 and 1000 mg/kg/day. No noteworthy signs of toxicity were noted in feeding or body wt., functional observational battery or motor activity. Gross necropsy and clin. chem. did not reveal any effects on organ mass or blood chem. and microscopic examns. found no lesions assocd. with treatment. Therefore, TARRALIN appears to be safe and non-toxic in these studies and a no-obsd. adverse effect level in rats is established at 1000 mg/kg/day.
(Comment this)
Antihyperglycemic activity of Tarralin, an ethanolic extract of Artemisia dracunculus L.
Ribnicky D M; Poulev A; Watford M; Cefalu W T; Raskin I
Biotech Center, Cook College, Rutgers University, 59 Dudley Road, New Brunswick, NJ 08901-8520, USA. ribnicky@aesop.rutgers.edu
Phytomedicine : international journal of phytotherapy and phytopharmacology (2006), 13(8), 550-7.
Journal code: 9438794. ISSN:0944-7113. Germany: Germany, Federal Republic of. Journal; Article; (JOURNAL ARTICLE); (RESEARCH SUPPORT, N.I.H., EXTRAMURAL); (RESEARCH SUPPORT, NON-U.S. GOV'T) written in English. PubMed ID 16920509 AN 2006496574 MEDLINE
Abstract
The studies reported here were undertaken to examine the antihyperglycemic activity of an ethanolic extract of Artemisia dracunculus L., called Tarralin in diabetic and non-diabetic animals. In genetically diabetic KK-A(gamma) mice, Tarralin treatment by gavage (500 mg/kg body wt./day for 7 days) lowered elevated blood glucose levels by 24% from 479+/-25 to 352+/-16 mg/dl relative to control animals. In comparison, treatment with the known antidiabetic drugs, troglitazone (30 mg/kg body wt./day) and metformin (300 mg/kg body wt./day), decreased blood glucose concentrations by 28% and 41%, respectively. Blood insulin concentrations were reduced in the KK-A(gamma) mice by 33% with Tarralin, 48% with troglitazone and 52% with metformin. In (STZ)-induced diabetic mice, Tarralin treatment, (500 mg/kg body wt./day for 7 days), also significantly lowered blood glucose concentrations, by 20%, from 429+/-41 to 376+/-58 mg/dl relative to control. As a possible mechanism, Tarralin was shown to significantly decrease phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression by 28% in STZ-induced diabetic rats. In non-diabetic animals, treatment with Tarralin did not significantly alter PEPCK expression, blood glucose or insulin concentrations. The extract was also shown to increase the binding of glucagon-like peptide (GLP-1) to its receptor in vitro. These results indicate that Tarralin has antihyperglycemic activity and a potential role in the management of diabetic states.
(Comment this)
Yes, they are conducting real trials. Since it is from an herb, they probably could just market their product as a supplement or nutriceutical (and avoid the FDA), but they want to have scientific evidence to back it up.
I wonder how different Russian Tarragon is from the Tarragon we have in the US?
(Comment this)
I am excited IRS2 mechanism regardless of whether or not Tarragon is the right stuff. Tarragon increases the binding of GLP1, improves insulin sensitivity in a new way, and complements motorman, etc. The Bayetta and Januvia should be interested in GLP1 help.
The dosage to the mice was massive and cannot scale to humans, but results are spectacular in 7 days. The FDA trials usually show improvements over a 24-week trial, so I think it would be reasonable to expect lower dosages over the long run to be effective. The trial seems more interested in establishing the safety features of the product. Results in 7 days means that this stuff can work quickly and show results. If this stuff works for your, we should expect quick results, or none at all. If it does not show results quickly stop using it.
The genecard identified as interacting with IGF1R. My research indicates HGH and IGF1 occur in a pulse in the morning at times of low blood sugar. The mechanisms of action seems to indicate that phosphatidylinositol and tyrosine. Arginine supplementation is beneficial to HGH and IGF1 production.
Insmed in past years was in trials using IGF1 instead of insulin for blood sugar control. I think the results were erratic and did not make it through the trials. My estimation is that IGF1 can potentially take approximately 20% of the glucose uptake while 80% comes from insulin.
(Comment this)
It does sound promising, but there is more study needed. I hope it pans out.
(Comment this)
----
.beta.-cell failure in diabetes and preservation by clinical treatment.
Wajchenberg, Bernardo L.
Endocrine Service and Diabetes and Heart Center of The Heart Institute, Hospital das Clinicas of The University of Sao Paulo Medical School, Sao Paulo, Brazil.
Endocrine Reviews (2007), 28(2), 187-218.
Publisher: Endocrine Society, CODEN: ERVIDP ISSN: 0163-769X. Journal written in English. AN 2007:493443
Abstract
There is a progressive deterioration in .beta.-cell function and mass in type 2 diabetics. It was found that islet function was about 50% of normal at the time of diagnosis, and a redn. in .beta.-cell mass of about 60% was shown at necropsy. The redn. of .beta.-cell mass is attributable to accelerated apoptosis. The major factors for progressive loss of .beta.-cell function and mass are glucotoxicity, lipotoxicity, proinflammatory cytokines, leptin, and islet cell amyloid. Impaired .beta.-cell function and possibly .beta.-cell mass appear to be reversible, particularly at early stages of the disease where the limiting threshold for reversibility of decreased .beta.-cell mass has probably not been passed. Among the interventions to preserve or "rejuvenate" .beta.-cells, short-term intensive insulin therapy of newly diagnosed type 2 diabetes will improve .beta.-cell function, usually leading to a temporary remission time. Another intervention is the induction of .beta.-cell "rest" by selective activation of ATP-sensitive K+ (KATP) channels, using drugs such as diazoxide. A third type of intervention is the use of antiapoptotic drugs, such as the thiazolidinediones (TZDs), and incretin mimetics and enhancers, which have demonstrated significant clin. evidence of effects on human .beta.-cell function. The TZDs improve insulin secretory capacity, decrease .beta.-cell apoptosis, and reduce islet cell amyloid with maintenance of neogenesis. The TZDs have indirect effects on .beta.-cells by being insulin sensitizers. The direct effects are via peroxisome proliferator-activated receptor .gamma. activation in pancreatic islets, with TZDs consistently improving basal .beta.-cell function. These beneficial effects are sustained in some individuals with time. There are several trials on prevention of diabetes with TZDs.
Incretin hormones, which are released from the gastrointestinal tract in response to nutrient ingestion to enhance glucose-dependent insulin secretion from the pancreas, aid the overall maintenance of glucose homeostasis through slowing of gastric emptying, inhibition of glucagon secretion, and control of body wt. From the two major incretins, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), only the first one or its mimetics or enhancers can be used for treatment because the diabetic .beta.-cell is resistant to GIP action. Because of the rapid inactivation of GLP-1 by dipeptidyl peptidase (DPP)-IV, several incretin analogs were developed: GLP-1 receptor agonists (incretin mimetics) exenatide (synthetic exendin-4) and liraglutide, by conjugation of GLP-1 to circulating albumin. The acute effect of GLP-1 and GLP-1 receptor agonists on .beta.-cells is stimulation of glucose-dependent insulin release, followed by enhancement of insulin biosynthesis and stimulation of insulin gene transcription. The chronic action is stimulating .beta.-cell proliferation, induction of islet neogenesis, and inhibition of .beta.-cell apoptosis, thus promoting expansion of .beta.-cell mass, as obsd. in rodent diabetes and in cultured .beta.-cells. Exenatide and liraglutide enhanced postprandial .beta.-cell function. The inhibition of the activity of the DPP-IV enzyme enhances endogenous GLP-1 action in vivo, mediated not only by GLP-1 but also by other mediators. In preclin. studies, oral active DPP-IV inhibitors (sitagliptin and vildagliptin) also promoted .beta.-cell proliferation, neogenesis, and inhibition of apoptosis in rodents. Meal tolerance tests showed improvement in postprandial .beta.-cell function. Obviously, it is difficult to est. the protective effects of incretin mimetics and enhancers on .beta.-cells in humans, and there is no clin. evidence that these drugs really have protective effects on .beta.-cells.
(Comment this)
(Comment this)
I have been looking at Tarragon and IRS2 and IRS2 insulin resistance. My research is leading to myo-inositol-hexaphosphate and d-chiro-inositol. When looking at the research these inositol's are always mentionsed in POCS. The science is better for POCS than anything else. Please read everything you can on inositol isomers. There is no toxicity, in fact inositol is a comercial emulsifier.
(Comment this)
Mmostof what I have googledso far is way over my head in comprehending...do we with PCOS not have enough of this/these...I see a lot of relations to seafood....is there a correlation to iodine (I amanaphlaticly allergic)??
(Comment this)
Scientists Find Way to Block Weight Gain in Stressed People
Monday , July 02, 2007
By Marrecca Fiore
In the quest for a perfect body, what if humans were able to lose a little weight here, while gaining a little weight there?
Scientists from Georgetown University Medical Center have found that blocking the pathway that leads stressed people to gain weight is the key to manipulating fat — at least in laboratory animals.
The findings, published online in Nature Medicine on Sunday, explain why people who are chronically stressed often develop "metabolic syndrome," a condition which causes individuals to gain more weight than they should based on the calories they consume.
Sixty million Americans were estimated to be affected by metabolic syndrome in 2000, according to a study funded by the Centers for Disease Control and Prevention in 2004.
This pathway, according to researchers, involves two players − a neurotransmitter (neuropeptide Y, or NPY) and the receptor (neuropeptide Y2 receptor, or Y2R), which activate in two types of cells in the fat tissue: endothelial cells lining blood vessels and fat cells themselves.
The researchers found that both NPY and Y2R are activated during stress, leading to apple-shape obesity and metabolic syndrome.
With this understanding, researchers were able to add fat selectively to the mice by injecting NPY into a specific area. They were also able to block weight gain and metabolic syndrome by injecting the mice with Y2R blocker into the abdominal fat.
"We couldn’t believe such fat remodeling was possible, but the numerous different experiments conducted over four years demonstrated that it is, at least in mice; recent pilot data also suggest that a similar mechanism exist in monkeys as well," said the study’s senior author, Zofia Zukowska, M.D., Ph.D., professor and chairman of the Department of Physiology & Biophysics at Georgetown University Medical Center, in a news release.
For the study, stressed animals fed a normal diet did not gain weight, but stressed mice given a high-fat diet did. The researchers found these mice put on more weight than expected given the calories they were consuming.
"They gained twice as much fat as would be expected, and it was all in their belly area," said Lydia Kuo, a medical student who earned her Ph.D. in physiology due to work on the study, also in a news release.
Stressed versus non-stressed animals ate the same amount of food, but the stressed animals processed it differently, she said, adding, "the novel finding here is that NPY works on fat tissue, not in the brain."
"We are hopeful that these findings might eventually lead to control of metabolic syndrome, which is a huge health issue for many Americans," Zukowska said. "Decreasing fat in the abdomen of the mice we studied reduced the fat in their liver and skeletal muscles, and also helped to control insulin resistance, glucose intolerance, blood pressure and inflammation. Blocking Y2R might work the same way in humans, but much study will be needed to prove that."
The fat is most likely stored to give the stressed mice an evolutionary advantage, Zukowska said.
"If you can store fat for times of hardship, you have a fat reserve that can be turned into energy for the next fight," she said. "The same mechanism may be happening in humans. An accumulation of chronic stressors, like disagreements with your boss, taking care of a chronically ill child, or repeated traffic road rages, could be acting as an amplifier to a hypercaloric diet when protracted over time. Depression may also be acting as a stressor."
The research could lead to clinical uses in cosmetic and reconstructive plastic surgery, said co-author Stephen Baker, M.D., D.D.S, associate professor of plastic surgery at Georgetown University Hospital. The ability to add fat as a graft would be useful for facial rejuvenation, breast surgery, buttock and lip enhancement, and facial reconstruction, he said, and using injections like those tested in this study could make fat grafts predictable, inexpensive, biocompatible and permanent, he said.
"This is the first well-described mechanism found that can effectively eliminate fat without using surgery," Baker said. "A safe, effective, non-surgical means to eliminate undesirable body fat would be of great benefit to our patients."
Investigators say these findings may also, over the long-term, lead to better control of metabolic syndrome, which carries risk factors that increase a patient’s chances of developing heart disease, stroke, and diabetes.
http://www.foxnews.com/story/0,2933,287686,00.html
(Comment this)
-----
Neuropeptide Y5 receptor antagonism does not induce clinically meaningful weight loss in overweight and obese adults.
Erondu, Ngozi; Gantz, Ira; Musser, Bret; Suryawanshi, Shailaja; Mallick, Madhuja; Addy, Carol; Cote, Josee; Bray, George; Fujioka, Ken; Bays, Harold; Hollander, Priscilla; Sanabria-Bohorquez, Sandra M.; Eng, WaiSi; Langstrom, Bengt; Hargreaves, Richard J.; Burns, H. Donald; Kanatani, Akio; Fukami, Takehiro; MacNeil, Douglas J.; Gottesdiener, Keith M.; Amatruda, John M.; Kaufman, Keith D.; Heymsfield, Steven B.
Merck and Co., Inc., Rahway, NJ, USA.
Cell Metabolism (2006), 4(4), 275-282.
Publisher: Cell Press, CODEN: CMEEB5 ISSN: 1550-4131. Journal written in English. CAN 145:410412
Abstract
Neuropeptide Y (NPY) is a potent orexigenic neuropeptide, and antagonism of NPY Y1 and NPY Y5 receptors (NPYxR) is considered a potentially important anti-obesity drug target. The authors tested the hypothesis that blockade of the NPY5R will lead to wt. loss in humans using MK-0557, a potent, highly selective, orally active NPY5R antagonist. The initial series of expts. reported herein, including a multiple-dose positron-emission tomog. study and a 12-wk proof-of-concept/dose-ranging study, suggested an optimal MK-0557 dose of 1 mg/day. The hypothesis was then tested in a 52-wk, multicenter, randomized, double-blind, placebo-controlled trial involving 1661 overweight and obese patients. Although significant at 52 wk, the magnitude of induced wt. loss was not clin. meaningful. These observations provide the first clin. insight into the human NPY-energy homeostatic pathway and suggest that solely targeting the NPY5R in future drug development programs is unlikely to produce therapeutic efficacy.
(Comment this)