July 9, 2020

Keeping beta cells “fit”

Vanderbilt cell biologists are defining the factors that help beta cells in the pancreas stay healthy, secrete insulin and prevent diabetes initiation and progression.

by Leigh MacMillan

The proteins Sin3a and Sin3b act as scaffolds for protein complexes that regulate gene expression to control cell differentiation, survival and function.

Guoqiang Gu, PhD, and colleagues have assessed the roles of Sin3a/b in the embryonic development and postnatal function of pancreatic insulin-secreting beta cells.

They discovered that mice missing Sin3a in endocrine progenitor cells (cells that give rise to pancreatic islets) gradually developed diabetes after birth. Sin3a-deficient beta cells had defective insulin secretion, cell survival, calcium influx and insulin vesicle biogenesis. The researchers showed that inactivation of both Sin3a and Sin3b further reduced islet cell mass at birth, and they identified target genes for Sin3a regulation in beta cells.

The findings, reported in the June issue of the journal Diabetes, show that Sin3 proteins play essential roles in islet cell production and postnatal beta cell “fitness.” Strategies that modulate Sin3a levels or activity might protect beta cell fitness and prevent diabetes initiation and progression.

This research wassupported by grants from the National Institutes of Health (DK106228, DK103831, CA095103, DK065949) and JDRF.