Abstract
Insulin-induced hypoglycemia is a major limiting factor in maintaining optimal blood glucose in patients with type 1 diabetes and advanced type 2 diabetes. Luckily, a counterregulatory response (1) system exists to help minimize and reverse hypoglycemia, although more studies are needed to better characterize its components. Recently, we showed that the hormone ghrelin is permissive for the normal CRR to insulin-induced hypoglycemia when assessed in mice without diabetes. Here, we tested the hypothesis that ghrelin also is protective against insulin-induced hypoglycemia in the streptozotocin (2) mouse model of type 1 diabetes. STZ-treated ghrelin-knockout (KO) (3) mice as well as STZ-treated wild-type (WT) littermates were subjected to a low-dose hyperinsulinemic-hypoglycemic clamp procedure. The STZ-treated ghrelin-KO mice required a much higher glucose infusion rate than the STZ-treated WT mice. Also, the STZ-treated ghrelin-KO mice exhibited attenuated plasma epinephrine and norepinephrine responses to the insulin-induced hypoglycemia. Taken together, our data suggest that without ghrelin, STZ-treated mice modeling type 1 diabetes are unable to mount the usual CRR to insulin-induced hypoglycemia.
Highlights
Insulin-induced hypoglycemia is prevalent in type 1 diabetes and advanced type 2 diabetes [4]
We investigated the contributions of ghrelin to the counterregulatory response (CRR) to insulin-induced hypoglycemia using mice without diabetes [41]
A single high-dose of STZ (150 mg/Kg, i.p.) was administered to both ghrelin-KO mice and WT littermates in order to model type 1 diabetes mellitus
Summary
Insulin-induced hypoglycemia is prevalent in type 1 diabetes and advanced type 2 diabetes [4]. Given the high risk of morbidity and mortality associated with hypoglycemia, mammals have developed a highly integrated counterregulatory response (CRR) system to help prevent, minimize, and reverse hypoglycemia. This CRR system is mobilized to varying degrees during progression from fasting to starvation. As reviewed by Cryer [5], in humans, the first defense within the traditional CRR involves decreased insulin secretion, which disinhibits glycogenolysis and gluconeogenesis and reduces glucose uptake into muscle and fat. The second defense involves increased glucagon release, stimulating hepatic glycogenolysis and gluconeogenesis. The third defense is an increase in epinephrine, resulting in higher delivery of gluconeogenic substrates to the liver and inhibition of whole body glucose utilization and insulin
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
