Gastric Receptor Blockade Reduces Insulin Resistance

Ablation of the gastric inhibitory polypeptide receptor (GIP-R) leads to reduced insulin resistance and a variety of other beneficial effects.

Dr. Peter R. Flatt, Senior investigator stated that "our research strongly suggests that GIP-R antagonists could represent an important new class of drugs for the treatment of insulin resistance, which underlies type 2 diabetes, obesity and other major diseases of the metabolic syndrome."

Dr. Flatt of the University of Ulster, Coleraine, Northern Ireland, and colleagues gave young adult obese diabetic mice saline or an injection of a GIP-R antagonist once daily over an 11-day period.

In antagonist-treated mice, nonfasting glucose levels and the overall glycemic excursion in response to a glucose load were significantly reduced. Treatment also lowered overall plasma glucose and insulin response to feeding and significantly enhanced insulin sensitivity.

Moreover, therapy reduced pancreatic insulin content and partially corrected the animals’ obesity-related islet hypertrophy and beta-cell hyperplasia.

These effects, say the investigators, were reversed 9 days after stopping treatment and were independent of body weight and food intake, both of which remained unchanged.

Thus continued Dr. Flatt, "the discovery that GIP-R antagonists are effective blood glucose-lowering agents which improve insulin action and ameliorate the characteristic deterioration of insulin-secreting pancreatic beta cells in diabetes has very significant clinical implications."

"We are hopeful," he added, "that further clinical trials will establish GIP-R antagonists as effective and safe tools for future treatment of the emerging human type 2 diabetes and obesity epidemic."

In fact, he concluded the he and his colleagues "anticipate that we will have our lead drug compound in the clinic by early 2007."
Diabetes 2005;54:2436-2446.

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DID YOU KNOW:
A Spoonful of Sugar is Sufficient for Diabetic Atherosclerosis: Study shows that hyperglycemia alone can accelerate atherosclerosis. People with diabetes are more likely to develop atherosclerosis, leading to more heart attacks and strokes in this population. But evidence that hyperglycemia in these patients contributes to atherosclerosis was lacking. In the study it showed that hyperglycemia alone can accelerate atherosclerosis. The researchers create mice lacking a gene called aldose reductase (AR) that mediates the generation of toxic products from glucose and cross these mice with atherosclerosis-prone mice lacking a protein called Ldlr. They found that AR expression modulates atherosclerosis development in the diabetic animals. Thus, inhibitors of AR or other proteins that mediate glucose toxicity may be useful for treating diabetic atherosclerosis. Journal of Clinical Investigation,Sept. 1, 2005 View the PDF of this article at: https://www.the-jci.org/article.php?id=24819

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