β Cell GHS-R Regulates Insulin Secretion and Sensitivity

Area of Science:

• Endocrinology
• Metabolism
• Molecular Biology

Background:

• The growth hormone secretagogue receptor (GHS-R) is known for regulating food intake and adiposity.
• Its precise role in glucose homeostasis and pancreatic islet function remains largely unclear.

Purpose of the Study:

• To investigate GHS-R expression in mouse pancreatic islets.
• To elucidate the function of GHS-R in glycemic regulation and insulin secretion.

Main Methods:

• Utilized Ghsr-IRES-tauGFP mice to visualize GHS-R expression via Green Fluorescent Protein (GFP) co-localization with insulin and glucagon.
• Generated β-cell-specific GHSR-deleted mice (MIP-Cre/ERT;Ghsr^f/f) to assess the impact of GHS-R deletion on glucose metabolism.
• Performed glucose tolerance tests (GTT), glucose-stimulated insulin secretion (GSIS) tests in vivo and ex vivo, and insulin tolerance tests (ITT).

Main Results:

• Confirmed GHS-R expression in pancreatic β and α cells.
• Mice lacking GHS-R in β cells (MIP-Cre/ERT;Ghsr^f/f) exhibited normal energy homeostasis but displayed significant alterations in glucose metabolism.
• These mice showed lower fasting glucose and insulin levels, reduced insulin secretion in response to glucose, and improved insulin sensitivity.
• GHS-R was found to cell-autonomously regulate glucose-stimulated insulin secretion and modulate systemic insulin sensitivity.

Conclusions:

• β cell GHS-R plays a critical role in regulating glucose homeostasis.
• GHS-R antagonists represent a potential therapeutic strategy for managing Type 2 Diabetes.