A potential role for GPR107 in hypoglycemia unawareness

Abstract

Hypoglycemia unawareness (HU) is a major barrier to achieving glycemic control in diabetic patients and remains a severe complication for type 1 and many type 2 diabetics. Due to the limited availability of animal models and significant variations between existing models, our understanding is limited regarding the cellular mechanisms and neural pathways responsible for this loss of metabolic control in the setting of recurrent hypoglycemia. Our group has recently identified GPR107 as a receptor for neuronostatin (NST), a 13 amino acid peptide derived from the somatostatin prepro-hormone. In our novel rat model of HU, we show that GPR107 expression is dramatically increased in the hypothalamus of rats exhibiting loss of hypoglycemia-induced food intake. Using a GPR107-flox rat model, we evaluated the effect of loss of GPR107 in the hypothalamus on the development of HU. Our preliminary data indicate that knockdown of hypothalamic GPR107 protects rats against HU induced by exposure to recurrent hypoglycemia. Future work will focus on the mechanisms underlying the role of GPR107 in the development of this dangerous clinical entity. National Institute of Health (NIH) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.