Insulin Resistance Alters Islet Morphology in Nondiabetic Humans

  1. Rohit N. Kulkarni1
  1. 1Islet Cell Biology & Regenerative Medicine, Joslin Diabetes Center, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
  2. 2Division of Endocrinology and Metabolic Diseases, Università Cattolica del Sacro Cuore, Rome, Italy
  3. 3Department of Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
  4. 4Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, the Panum Institute, University of Copenhagen, Denmark
  5. 5Fondazione Don Gnocchi, Milan, Italy
  1. Corresponding authors: Andrea Giaccari, giaccari{at}, and Rohit N. Kulkarni, rohit.kulkarni{at}


Type 2 diabetes is characterized by poor glucose uptake in metabolic tissues and manifests when insulin secretion fails to cope with worsening insulin resistance. In addition to its effects on skeletal muscle, liver, and adipose tissue metabolism, it is evident that insulin resistance also affects pancreatic β-cells. To directly examine the alterations that occur in islet morphology as part of an adaptive mechanism to insulin resistance, we evaluated pancreas samples obtained during pancreatoduodenectomy from nondiabetic subjects who were insulin-resistant or insulin-sensitive. We also compared insulin sensitivity, insulin secretion, and incretin levels between the two groups. We report an increased islet size and an elevated number of β- and α-cells that resulted in an altered β-cell–to–α-cell area in the insulin- resistant group. Our data in this series of studies suggest that neogenesis from duct cells and transdifferentiation of α-cells are potential contributors to the β-cell compensatory response to insulin resistance in the absence of overt diabetes.


  • Received June 28, 2013.
  • Accepted November 6, 2013.

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