Islets in Type 2 Diabetes: In Honor of Dr. Robert C. Turner

  1. Susan Bonner-Weir1 and
  2. Timothy D. O'Brien2
  1. 1Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts
  2. 2Department of Veterinary Population Medicine and Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota
  1. Corresponding authors: Susan Bonner-Weir, susan.bonner-weir{at}joslin.harvard.edu, and Timothy D. O'Brien, obrie004{at}umn.edu

The UK Prospective Diabetes Study (UKPDS) orchestrated by Robert Turner showed that, even with treatment, in type 2 diabetes a progressive β-cell dysfunction in a large number of patients was seen with the eventual need for additional oral antihyperglycemic medication and even insulin treatment (1). Such a progression could be from a continued loss of β-cells, a progressive functional change, or from the combination of both. During the decades when type 2 diabetes was considered mainly a disease of insulin resistance, many older pathology studies that focused on the islets in diabetic pancreata were ignored. However, with the renewed appreciation of the role of the pancreatic β-cell in type 2 diabetes, new studies have focused on what happens to the β-cells in type 2 diabetes. This perspectives in diabetes article will present what we know and still need to know about the islets in type 2 diabetes.

Islet architecture in human pancreas.

The islets of most mammalian species have a nonrandom pattern with a core of β-cells surrounded by a discontinuous mantle of non-β-cells one to three cells thick (2,3). However, islets of human and other primates have a more complex arrangement with many different islet profiles, including cloverleaf patterns. The profile differences have led to controversy about whether they actually have a mantle-core arrangement (3) or were random (4–6). In three dimensions, human islets can be considered as composites of several mantle-core subunits (7) or as lobulated with mantle-core lobules (3). In smaller islets, the rodent mantle core subunit arrangement is maintained, but in larger islets irregular fusion of such subunits are seen (Fig. 1). Most of the non-β-cells are found along penetrations of islet vasculature between subunits and the periphery (3,4), thus maintaining a mantle-core arrangement. Histologically, islets in the type 2 diabetic pancreas do not appear …

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