Hormone Blocker Fights Obesity And Diabetes
… in mice!A new study finds that a chemical found in the body is capable of promoting weight loss, improving insulin resistance and reversing diabetes in an animal model. The compound is blocking the gastric inhibitory polypeptide (GIP) receptor.GIP is a peptide hormone that is secreted in response to food. It inhibits the secretion of acids stimulates the releases insulin as part of the digestive process in response to food. It is found in a variety of tissues, including the intestine, heart, stomach, brain and in adipose (fat).While the significance of its action is largely unknown, its potent and prolonged stimulation after a high-fat diet has led researchers to speculate it may play a key role in metabolizing fat. Research has shown that high fat feeding results in elevated circulating GIP concentrations, traits often found in patients who are obese with diabetes. GIP also effects the growth of fat cells. Other studies have shown that mice injected with the GIP receptor antagonist – (Pro3)GIP – can reverse or prevent many of the metabolic abnormalities associated with obesity.
This new study examined whether prolonged GIP receptor antagonism using daily injections of (Pro3) GIP was able to reverse well established diet-induced obesity and related metabolic abnormalities.he researchers used a mouse model for diet-induced obesity that has been used extensively alongside genetic models and has close parallels with obesity, increasingly found in humans who consume a high-fat, energy-rich diet. IKey Findings
Highlights of the research findings include the following:
- Compared with the standard rodent diet (control), the mice that were fed the high-fat diet for the previous 160 days exhibited increased body weight, energy intake, and circulating glucose concentrations. The levels remained elevated throughout the study. The cholesterol and triglycerides levels increased at day 50.
- Consumption of the high fat diet resulted in progressive weight gain and elevations of plasma glucose and gyrated hemoglobin, leading to impaired insulin sensitivity and glucose intolerance by 10 days. Fat (adipose) tissue deposits were increased as were circulating cholesterol and triglyceride concentration levels.
- (Pro3)GIP was able to counter many of the detrimental effects of high fat diet on body weight and indices of glucose and lipid metabolism.
This study showed that blocking GIP activity using (Pro3)GIP in mice with established, high fat diet-induced obesity and diabetes results in significant weight loss, improvement of insulin resistance and amelioration of diabetes. These findings represent an interesting new approach to the treatment of obesity and metabolic disturbances.
According to Nigel Irwin, Ph.D., “Interestingly, possible parallels exist with the benefits of Roux-en-Y surgery (gastric bypass surgery) in treating gross obesity and associated diabetes in people. In this procedure, nutrients surgically bypass the area of the small intestine, resulting in a deficiency of circulating GIP. We are looking to better understand how and why.”Am J Physiol Endocrinol Metab. 2007 Dec;293(6):E1746-55. Epub 2007 Sep 11.
School of Biomedical Sciences, Univ. of Ulster, Coleraine, Northern Ireland, BT52 1SA, United Kingdom. firstname.lastname@example.org).
The gut hormone gastric inhibitory polypeptide (GIP) plays a key role in glucose homeostasis and lipid metabolism. This study investigated the effects of administration of a stable and specific GIP receptor antagonist, (Pro(3))GIP, in mice previously fed a high-fat diet for 160 days to induce obesity and related diabetes. Daily intraperitoneal injection of (Pro(3))GIP over 50 days significantly decreased body weight compared with saline-treated controls, with a modest increase in locomotor activity but no change of high-fat diet intake. Plasma glucose, glycated hemoglobin, and pancreatic insulin were restored to levels of chow-fed mice, and circulating triglyceride and cholesterol were significantly decreased. (Pro(3))GIP treatment also significantly decreased circulating glucagon and corticosterone, but concentrations of GLP-1, GIP, resistin, and adiponectin were unchanged. Adipose tissue mass, adipocyte hypertrophy, and deposition of triglyceride in liver and muscle were significantly decreased. These changes were accompanied by significant improvement of insulin sensitivity, meal tolerance, and normalization of glucose tolerance in (Pro(3))GIP-treated high-fat-fed mice. (Pro(3))GIP concentrations peaked rapidly and remained elevated 24 h after injection. These data indicate that GIP receptor antagonism using (Pro(3))GIP provides an effective means of countering obesity and related diabetes induced by consumption of a high-fat, energy-rich diet.