Impact of non-alcoholic fatty pancreas disease on glucose metabolism

Abstract

With the increasing global epidemic of obesity, the clinical importance of non-alcoholic fatty pancreas disease (NAFPD) has grown. Even though the pancreas might be more susceptible to ectopic fat deposition compared with the liver, NAFPD is rarely discussed because of the limitation of detection techniques. In the past, NAFPD was considered as an innocent condition or just part of clinical manifestations during the course of obesity. Recently, a growing body of research suggests that NAFPD might be associated with β-cell dysfunction, insulin resistance and inflammation, which possibly lead to the development of diabetes and metabolic syndrome. The present review summarized the current literature on the epidemiology, potential pathophysiology, diagnostic techniques, impact of NAFPD on β-cell function and insulin resistance, and the clinical relevance of the interplay between NAFPD and glucometabolic disorders.

Keywords: Diabetes mellitus; Metabolic syndrome; Non-alcoholic fatty pancreas disease.

Figure 1

A potential interplay between dysglycemia, non‐alcoholic fatty pancreas disease (NAFPD) and β‐cell dysfunction. During long‐term intake of excessive calories, dietary fatty acids and hyperinsulinemia stimulate hepatic steatosis, leading to increased export of very‐low‐density lipoprotein (VLDL), which will increase fat delivery to the islets. In β‐cells, hyperglycemia inhibits carnitinine‐palmitoyl transferase‐1 (CPT‐1) through increasing malonyl coenzyme A (malonyl CoA), decreasing mitochondria β‐oxidation and further promoting intracellular triglyceride (TG) accumulation. In contrast, insulin resistance enhances triglyceride lipolysis and free fatty acid (FFA) release from visceral adipose tissue (VAT), thus increasing circulating FFAs. Chronic exposure of β‐cell to elevated FFAs results in increased intracellular triacylglycerol content, decreased insulin gene expression and blunted glucose‐stimulated insulin secretion. In addition, adipocyte‐derived cytokines and FFAs also contribute to β‐cell destruction, which further blunts insulin secretion as well as promotes intrapancreatic replacement by adipocytes. When fat deposition in the pancreas exceeds the tolerance threshold, hyperglycemia will supervene and causes a vicious cycle of continuous deterioration of glucometabolic state. DG, diglycerides; PA, phosphatidic acid; TCA, tricarboxylic acid.