Direct Autocrine Action of Insulin on β-Cells: Does It Make Physiological Sense?

  1. Steven E. Kahn4
  1. 1Kovler Diabetes Center, Department of Medicine, University of Chicago, Chicago, Illinois
  2. 2Division of Endocrinology, Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts
  3. 3Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Vermont, Colchester, Vermont
  4. 4Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle, Washington
  1. Corresponding author: Christopher J. Rhodes, cjrhodes{at}uchicago.edu.

Abstract

In recent years there has been a growing interest in the possibility of a direct autocrine effect of insulin on the pancreatic β-cell. Indeed, there have been numerous intriguing articles and several eloquent reviews written on the subject (13); however, the concept is still controversial. Although many in vitro experiments, a few transgenic mouse studies, and some human investigations would be supportive of the notion, there exist different insights, other studies, and circumstantial evidence that question the concept. Therefore, the idea of autocrine action of insulin remains a conundrum. Here we outline a series of thoughts, insights, and alternative interpretations of the available experimental evidence. We ask, how convincing are these, and what are the confusing issues? We agree that there is a clear contribution of certain downstream elements in the insulin signaling pathway for β-cell function and survival, but the question of whether insulin itself is actually the physiologically relevant ligand that triggers this signal transduction remains unsettled.

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