UC Davis

Zinc transporter 8 (ZNT8), predominantly located in pancreatic β-cells, is essential for insulincrystallization and secretion. Its genetic variations are associated with heightened Type 2 Diabetes (T2D) risks. Somatostatin (SST), widely expressed in the brain and other tissues, including pancreatic islets, primarily functions as an inhibitory hormone. Within the pancreas, SST modulates glucose metabolism by affecting insulin and glucagon secretions. This study unravels the intricate roles of ZNT8 and SST in maintaining glucose and lipid metabolism. Our research explores the impacts of maternal Sst deficiency on the metabolic health trajectory of the progeny. Results indicate that descendants from mothers with Sst deficiencies experience hindered pancreatic islet development, rendering them more susceptible to diet-induced obesity and T2D. Further, we probed the concurrent effects of Znt8 and Sst deficits in mice on a high-fat regimen. Strikingly, the co-absence of Znt8 and Sst led to a pronounced disruption in insulin secretion compared to mice with isolated deficiencies. We also evaluated the influence of a prevalent variant (rs13266634) within the Znt8 gene on glucose metabolism and lipid parameters in 349 healthy participants. Our findings delineated that those with the CC genotype exhibit a reduced insulin response after a mixed macronutrient tolerance test. In contrast, carriers of the Tallele appear to experience delayed postprandial blood triglyceride clearance, particularly in male and overweight subjects. In summary, this research underscores the pivotal roles and significant interplay of Znt8 and Sst play in metabolic health. These findings would provide new research targets to uncover the role of ZNT8 and SST in the development of metabolic diseases, such as T2D and obesity.