Pancreatic adipocytes mediate hypersecretion of insulin in diabetes-susceptible mice

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 insulin resistance. 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 by IF.