Pancreatic adipocytes mediate hypersecretion of insulin in diabetes-susceptible mice

  • Charline Quiclet
    Affiliations
    Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany

    German Center for Diabetes Research (DZD), München-Neuherberg 85764, Germany
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  • Nicole Dittberner
    Affiliations
    Department of Adipocyte Development and Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany
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  • Anneke Gässler
    Affiliations
    Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany

    German Center for Diabetes Research (DZD), München-Neuherberg 85764, Germany
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  • Mandy Stadion
    Affiliations
    Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany

    German Center for Diabetes Research (DZD), München-Neuherberg 85764, Germany
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  • Felicia Gerst
    Affiliations
    German Center for Diabetes Research (DZD), München-Neuherberg 85764, Germany

    Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard Karls University of Tübingen, 72076, Tübingen, Germany
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  • Anett Helms
    Affiliations
    Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany

    German Center for Diabetes Research (DZD), München-Neuherberg 85764, Germany
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  • Christian Baumeier
    Affiliations
    Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany

    German Center for Diabetes Research (DZD), München-Neuherberg 85764, Germany
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  • Tim J. Schulz
    Affiliations
    German Center for Diabetes Research (DZD), München-Neuherberg 85764, Germany

    Institute for Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Eberhard Karls University of Tübingen, 72076, Tübingen, Germany

    Institute of Nutritional Science, University of Potsdam, 14558 Nuthetal, Germany
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  • Annette Schürmann
    Correspondence
    Corresponding author at: German Institute of Human Nutrition Potsdam-Rehbruecke (DifE), Department of Experimental Diabetology, Arthur-Scheunert-Allee114-116, 14558 Nuthetal, Germany.
    Affiliations
    Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany

    German Center for Diabetes Research (DZD), München-Neuherberg 85764, Germany

    Institute of Nutritional Science, University of Potsdam, 14558 Nuthetal, Germany
    Search for articles by this author

      Highlights

      • Diabetes-prone mice exhibit more pancreatic fat than diabetes-resistant mice.
      • Intermittent fasting prevents fatty pancreas and type 2 diabetes in NZO mice.
      • Pancreas-derived adipocytes alter islet insulin secretion.

      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 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.

      Abbreviations:

      AL (ad libitum), APCs (adipogenic precursor cells), AUC (area under the curve), FITC (fluorescein isothiocyanate), GSIS (glucose-stimulated insulin secretion), HFD (high-fat diet), IF (intermittent fasting), ipITT (intraperitoneal insulin tolerance test), iWAT (inguinal white adipose tissue), KRBH (Krebs-Ringer bicarbonate HEPES buffer), NAFLD (non-alcoholic fatty liver disease), NAFPD (non-alcoholic fatty pancreas disease), NEFA (non-esterified fatty acids), NZO (New Zealand Obese), ob/ob (B6.V-Lepob/ob), OGTT (oral glucose tolerance test), TG (triacylglycerol)
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