(P31-074-23) Lack of Maternal Exposure to Somatostatin Negatively Impacts the Development of Pancreas Islets Inducing Severe Insulin and Leptin Resistance in Offspring Fed a High-Fat Diet

Objectives: Somatostatin (SST) is a negative regulator of metabolic-related hormones, including insulin and glucagon. The prenatal environment plays an important role in the later development of type 2 diabetes in adulthood. The current study investigated the effects of maternal Sst deficiency in mice on adiposity and glucose metabolism in offspring with or without high-fat diet challenge, and the underlying mechanisms.

Methods: Male Sst-homozygous (SstKO) offspring born to Sst-heterozygous (SstHet) or SstKO mothers were fed either a regular chow diet (CD) or a high-fat diet (HFD) at 3 weeks of age for 15 weeks. Body weight and blood glucose (fasting and fed) levels were monitored during the feeding period. Glucose and insulin tolerance tests were performed, and the levels of fasting and postprandial metabolic-relevant hormones were determined.

Results: The offspring (SstKO-MSD) born to the SstKO dams gained more weights under the HFD than the SstKO and wild-type (WT) offspring born to the SstHet dams. Interestingly, the SstKO-MSD offspring fed the CD gained less weight (P < 0.05) and were more insulin sensitive (P < 0.05) than the SstKO and WT offspring. Moreover, the SstKO-MSD offspring fed the CD secreted less insulin (P < 0.05) than the SstKO and WT offspring during oral glucose tolerance test. A reduced islet/pancreas ratio was noticed in the pancreas of the SstKO-MSD mice than that of the SstKO and WT. We noticed that this reduced islet/pancreas ratio in the SstKO-MSD offspring rendered them to be more susceptible to the HFD-induced insulin resistance than the SstKO and WT offspring. Remarkably, we detected that the SstKO-MSD offspring were severe leptin resistance compared to the SstKO and WT offspring. Finally, we show that the SstKO and WT offspring had similar body weights, insulin sensitivity, and glucose tolerance when fed either the HFD or the CD.

Conclusions: Our findings demonstrate that lack of SST in the uterus may impair the development of islets of the pancreas in mice resulting in predisposition to severe diet-induced obesity and T2D. 

Funding Sources: This work was supported by the U.S. Department of Agriculture (USDA)/Agriculture Research Service (ARS)/Western Human Nutrition Research Center project funds (2032-51000-005-00D) and the Henry A. Jastro Scholarship awarded to Zhongyue Yang from University of California at Davis.