In type-2 diabetes, the overall incretin effect is reduced. Most important, the health benefits of Mediterranean diet have been attributed to the high intake of monounsaturated fat, mostly represented by extra virgin olive oil (EVOO). We investigated the role of PPARgamma in GIP-R transcription. “The main focus when it comes to DPP-4 inhibitors has been on GLP-1, which has been shown to have protective effects on the cardiovascular system, while little attention has been paid to potential effects of GIP, which is also affected by DPP-4 inhibitors”, says Professor Maria Gomez at Lund University, who led the study. However, only GLP-1 exerts insulinotropic properties when administered to patients with Type 2 diabetes. In this study, we investigated the presence of menin in K cells of the proximal duodenum and determined if it regulated the expression of GIP via PI3/AKT signaling in response to fasting and refeeding, and high-fat (HF) diet. Additional stimulation with GIP at 16 h did not affect cAMP generation, indicating desensitization of the GIP receptor by the ligand.
Finally, the Hybridtide® scaffold also provides for unique signalling capabilities we call Artisan Biology©. These findings suggest that the increased meal-stimulated GIP secretion in some patients with NIDDM is not due to a failure of insulin feedback on GIP secretion. Therefore, antagonistic analogues of GIP may be speculated to have a role in the pharmaceutical management of obesity.