Pancreatic Pericytes Support β-Cell Function in a Tcf7l2-Dependent Manner.

Area of Science:

• Endocrinology
• Cell Biology
• Genetics

Background:

• Polymorphism in TCF7L2 is linked to type 2 diabetes, but the underlying mechanism involving beta-cell dysfunction is unclear.
• Beta-cell function is influenced by their microenvironment, including pancreatic pericytes.

Purpose of the Study:

• To investigate the role of Tcf7l2 in pancreatic pericytes for beta-cell function.
• To elucidate the cellular and molecular mechanisms by which pericytic Tcf7l2 influences glucose homeostasis.

Main Methods:

• Utilized transgenic mice with selective Tcf7l2 inactivation in pancreatic pericytes.
• Assessed glucose tolerance, beta-cell function, and insulin secretion.
• Analyzed gene expression in isolated islets and identified secreted factors from pericytes.

Main Results:

• Selective inactivation of Tcf7l2 in pancreatic pericytes led to impaired glucose tolerance and compromised beta-cell function.
• Pericytic Tcf7l2 deficiency altered gene expression related to beta-cell function and maturity.
• Identified TCF7L2-dependent secretion of bone morphogenetic protein 4 (BMP4) by pericytes, which promotes beta-cell function.

Conclusions:

• Pancreatic pericyte Tcf7l2 activity is essential for maintaining beta-cell function and glucose homeostasis.
• Pericytes secrete factors like BMP4 in a TCF7L2-dependent manner to support beta-cells.
• Disruptions in the islet microenvironment, mediated by TCF7L2, may contribute to type 2 diabetes pathogenesis.