HDAC1 overexpression enhances β-cell proliferation by down-regulating Cdkn1b/p27.

The homeobox transcription factor Nkx6.1 is sufficient to increase functional β-cell mass, where functional β-cell mass refers to the combination of β-cell proliferation, glucose-stimulated insulin secretion (GSIS) and β-cell survival. Here, we demonstrate that the histone deacetylase 1 (HDAC1), which is an early target of Nkx6.

β-Hydroxybutyrate Elicits Favorable Mitochondrial Changes in Skeletal Muscle.

The clinical benefit of ketosis has historically and almost exclusively centered on neurological conditions, lending insight into how ketones alter mitochondrial function in neurons. However, there is a gap in our understanding of how ketones influence mitochondria within skeletal muscle cells. The purpose of this study was to elucidate the specific effects of β-hydroxybutyrate (β-HB) on muscle cell mitochondrial physiology.

β-Cell deletion of Nr4a1 and Nr4a3 nuclear receptors impedes mitochondrial respiration and insulin secretion.

β-Cell insulin secretion is dependent on proper mitochondrial function. Various studies have clearly shown that the Nr4a family of orphan nuclear receptors is essential for fuel utilization and mitochondrial function in liver, muscle, and adipose. Previously, we have demonstrated that overexpression of Nr4a1 or Nr4a3 is sufficient to induce proliferation of pancreatic β-cells.

Cdk5r1 Overexpression Induces Primary β-Cell Proliferation.

Decreased β-cell mass is a hallmark of type 1 and type 2 diabetes. Islet transplantation as a method of diabetes therapy is hampered by the paucity of transplant ready islets. Understanding the pathways controlling islet proliferation may be used to increase functional β-cell mass through transplantation or by enhanced growth of endogenous β-cells.

Aurora Kinase A is critical for the Nkx6.1 mediated β-cell proliferation pathway.

Type 1 and type 2 diabetes are ultimately characterized by depleted β-cell mass. Characterization of the molecular pathways that control β-cell proliferation could be harnessed to restore these cells. The homeobox β-cell transcription factor Nkx6.