Ghrelin differentially affects hepatic and peripheral insulin sensitivity in mice

Area of Science:

• Metabolic research
• Endocrinology
• Glucose metabolism

Background:

• Ghrelin, a peptide hormone, plays a role in appetite regulation.
• Its effects on glucose metabolism and insulin action are not fully understood.
• Investigating ghrelin's impact on insulin sensitivity is crucial for metabolic health research.

Purpose of the Study:

• To evaluate ghrelin's effects on insulin-mediated glucose production and disposal in mice.
• To determine if the growth hormone secretagogue (GHS) receptor mediates ghrelin's actions on insulin.
• To explore the role of des-ghrelin (unacylated ghrelin) in this context.

Main Methods:

• Intravenous infusion of ghrelin, GHRP-6, des-ghrelin, or vehicle in mice.
• Measurement of endogenous glucose production and glucose disposal using radiolabeled glucose during hyperinsulinemic-euglycemic clamp.
• Assessment of tissue-specific glucose uptake in muscle and adipose tissue.

Main Results:

• Ghrelin significantly increased glucose disposal and muscle glucose uptake.
• Ghrelin impaired insulin's ability to suppress endogenous glucose production.
• GHRP-6 had no effect on insulin action; des-ghrelin hindered hepatic insulin action.

Conclusions:

• Ghrelin modulates insulin action by enhancing glucose disposal and reducing hepatic insulin suppression, independent of food intake or body weight.
• These effects are likely not mediated by the GHS receptor.
• Des-ghrelin counteracts ghrelin's inhibitory effect on hepatic insulin action.