Lipid droplet accumulation in β cells in patients with type 2 diabetes is associated with insulin resistance, hyperglycemia and β cell dysfunction involving decreased insulin granules

Abstract

Background and objectivePancreatic fat is a form of ectopic fat. Lipid droplets (LDs) are also observed in β cells; however, the pathophysiological significance, especially for β cell function, has not been elucidated. Our aim was to assess LD accumulation in β cells in various stages of glucose intolerance and to clarify its relationship with clinical and histological parameters.MethodsWe examined 42 Japanese patients who underwent pancreatectomy. The BODIPY493/503-positive (BODIPY-positive) area in β cells was measured in pancreatic sections from 32 patients. The insulin granule numbers were counted in an additional 10 patients using electron microscopy.ResultsThe BODIPY-positive area in β cells in preexisting type 2 diabetes patients was higher than that in normal glucose tolerance patients (p = 0.031). The BODIPY-positive area in β cells was positively correlated with age (r = 0.45, p = 0.0097), HbA1c (r = 0.38, p = 0.0302), fasting plasma glucose (r = 0.37, p = 0.045), and homeostasis model assessment insulin resistance (r = 0.41, p = 0.049) and negatively correlated with an increase in the C-peptide immunoreactivity level by the glucagon test (r = -0.59, p = 0.018). The ratio of mature insulin granule number to total insulin granule number was reduced in the patients with rich LD accumulation in β cells (p = 0.039).ConclusionsType 2 diabetes patients had high LD accumulation in β cells, which was associated with insulin resistance, hyperglycemia, aging and β cell dysfunction involving decreased mature insulin granules.

Pathophysiological Mechanisms and Clinical Associations of Non-Alcoholic Fatty Pancreas Disease

“…21 In most cases, excessive weight gain gradually leads to the storage of surplus adipose tissue in non-adipose organs, including the pancreas, where fat accumulates intracellularly in both acinar and pancreatic islet cells, causing dysfunction. 21 The fatty replacement phase is characterized by an accumulation of intralobular fat in the form of lipid droplets in both endocrine and acinar cells, 34,35 provoking acinar cell…”

Association between Intrapancreatic Fat Deposition and Lower High-Density Lipoprotein Cholesterol in Individuals with Newly Diagnosed T2DM

“…Some studies found that IPFD was signifcantly associated with insulin resistance and β-cell function [13][14][15]; however, others hold a negative view [6,[16][17][18]. A recent study demonstrated that lipid droplet accumulation in β cells was associated with insulin resistance in T2DM individuals [19]. Ectopic fat deposition, including hepatic and pancreatic fat, was actuated by adipocyte dysfunction and elevated free fatty acids (FFAs) which were derived from triglyceride degradation, all of which might be involved in the process of insulin resistance [20].…”

Triglycerides and leptin soluble receptor: Which one is the target to protect β-cells in patients with type 2 diabetes?

“…concluded that accumulation of lipid droplets in β-cells was associated with insulin resistance which can lead to high levels of free fatty acids (FFAs) derived from degradation of triglycerides, the accumulated FFAs can flow into β-cell. In patients with T2DM due to insulin resistance, hyperglycemia combined with excess FFAs are linked to accumulation of lipid droplets in β-cell ( 16 ). Additionally, a longitudinal study which lasted for 15 years found that patients with familial combined hyperlipidemia were at high risk to develop T2DM ( 17 ).…”