The Impact of Glucagon to Support Post-Absorptive Glucose Flux and Glycemia in Healthy Rats and its Attenuation in Male Zucker Diabetic Fatty Rats

Am J Physiol Endocrinol Metab. 2024 Jan 24. doi: 10.1152/ajpendo.00192.2023. Online ahead of print.ABSTRACTHyperglucagonemia is a hallmark of type 2 diabetes (T2DM), yet the role of elevated plasma glucagon (P-GCG) to promote excessive post-absorptive glucose production and contribute to hyperglycemia in patients with this disease remains debatable. We investigated the acute action of P-GCG to safeguard/support post-absorptive endogenous glucose production (EGP) and euglycemia in healthy Zucker control lean (ZCL) rats. Using male Zucker diabetic fatty (ZDF) rats that exhibit the typical metabolic disorders of human T2DM, such as excessive EGP, hyperglycemia, hyperinsulinemia and hyperglucagonemia, we examined the ability of hyperglucagonemia to promote greater rates of post-absorptive EGP and hyperglycemia. Euglycemic or hyperglycemic basal insulin (INS-BC) and glucagon (GCG-BC) clamps were performed in the absence or during an acute setting of glucagon deficiency (GCG-DF, ~10% of basal), either alone or in combination with insulin deficiency (INS-DF, ~10% of basal). Glucose appearance, disappearance, and cycling rates were measured using [2-3H] and [3-3H]-glucose. In ZCL rats, GCG-DF reduced levels of hepatic cyclic AMP, EGP, and plasma glucose (PG) by 50, 32, and 50%, respectively. EGP fell in the presence GCG-DF and INS-BC, but under GCG-DF and INS-DF, EGP and PG increased two- and three-fold, respectively. GCG-DF revealed the hyperglucagonemia present in ZDF rats lacked t...
Source: American Journal of Physiology. Endocrinology and Metabolism - Category: Physiology Authors: Source Type: research