Pancreatic adipocytes mediate hypersecretion of insulin in diabetes-susceptible mice

Metabolism. 2019 Aug:97:9-17. doi: 10.1016/j.metabol.2019.05.005. Epub 2019 May 18.

Abstract

Objective: Ectopic fat accumulation in the pancreas in response to obesity and its implication on the onset of type 2 diabetes remain poorly understood. Intermittent fasting (IF) is known to improve glucose homeostasis and insulinresistance. However, the effects of IF on fat in the pancreas and β-cell function remain largely unknown. Our aim was to evaluate the impact of IF on pancreatic fat accumulation and its effects on islet function.

Methods: New Zealand Obese (NZO) mice were fed a high-fat diet ad libitum (NZO-AL) or fasted every other day (intermittent fasting, NZO-IF) and pancreatic fat accumulation, glucose homoeostasis, insulin sensitivity, and islet function were determined and compared to ad libitum-fed B6.V-Lepob/ob (ob/ob) mice. To investigate the crosstalk of pancreatic adipocytes and islets, co-culture experiments were performed.

Results: NZO-IF mice displayed better glucose homeostasis and lower fat accumulation in both the pancreas (-32%) and the liver (-35%) than NZO-AL mice. Ob/ob animals were insulin-resistant and had low fat in the pancreas but high fat in the liver. NZO-AL mice showed increased fat accumulation in both organs and exhibited an impaired islet function. Co-culture experiments demonstrated that pancreatic adipocytes induced a hypersecretion of insulin and released higher levels of free fatty acids than adipocytes of inguinal white adipose tissue.

Conclusions: These results suggest that pancreatic fat participates in diabetes development, but can be prevented byIF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism*
  • Adipose Tissue / metabolism
  • Animals
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diet, High-Fat / methods
  • Disease Models, Animal
  • Fasting / metabolism
  • Glucose / metabolism
  • Homeostasis / physiology
  • Insulin / metabolism*
  • Insulin Resistance / physiology
  • Insulin-Secreting Cells / metabolism
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Obese
  • Obesity / metabolism
  • Pancreas / metabolism*

Substances

  • Insulin
  • Glucose