The Potential Protective Action of Vitamin D in Hepatic Insulin Resistance and Pancreatic Islet Dysfunction in Type 2 Diabetes Mellitus

Abstract

Vitamin D deficiency (i.e., hypovitaminosis D) is associated with increased insulin resistance, impaired insulin secretion, and poorly controlled glucose homeostasis, and thus is correlated with the risk of metabolic diseases, including type 2 diabetes mellitus (T2DM). The liver plays key roles in glucose and lipid metabolism, and its dysregulation leads to abnormalities in hepatic glucose output and triglyceride accumulation. Meanwhile, the pancreatic islets are constituted in large part by insulin-secreting β cells. Consequently, islet dysfunction, such as occurs in T2DM, produces hyperglycemia. In this review, we provide a critical appraisal of the modulatory actions of vitamin D in hepatic insulin sensitivity and islet insulin secretion, and we discuss the potential roles of a local vitamin D signaling in regulating hepatic and pancreatic islet functions. This information provides a scientific basis for establishing the benefits of the maintenance, or dietary manipulation, of adequate vitamin D status in the prevention and management of obesity-induced T2DM and non-alcoholic fatty liver disease.

Keywords: HepG2; calcitriol; glucose homeostasis; hypovitaminosis D; insulin secretion; lipid metabolism.

Figure 1

Schematic representation of vitamin D synthesis and metabolism in relation to regulation of pancreatic islet function and survival.

Figure 2

Model of active vitamin D regulation of hepatic triglyceride accumulation and glucose output in a diabetic state.

Figure 3

Model of vitamin D in the regulation of pancreatic islet beta-cell function and survival in a diabetic state.