Changes in Islet Cell Composition During Development of Diabetes in Macaca nigra

Abstract

The islets of Langerhans in sections from the pancreas tail of Macaca nigra were stained by antiserum to insulin, glucagon, or somatostatin. The area of stained cells per total area of the islets was determined by a computerized photometric method. Insulin of the beta cells occupied 77% of the islet area in nondiabetic (ND) monkeys and decreased to 62% in monkeys in the earliest stages of metabolic deterioration, i.e., hormonally impaired (HI) monkeys. At the later stage of borderline diabetes (BD), monkeys had only 39% of the islet area occupied by insulin and the area was diminished to less than 1% in diabetic (D) monkeys. Islets in HI monkeys had an unusual pattern in which only the beta cells in the periphery of islets were stained. Glucagon in the alpha cells stained 7% of the islet area in ND monkeys, but the area was almost doubled to 13% in HI monkeys; the percentage decreased to about 5% in BD and 3% in D monkeys. Somatostatin accounted for 5% of the islet area in ND monkeys, was slightly greater at 7% in HI monkeys, and decreased to 3% in BD and 2% in D monkeys. Alterations in percentages of secretory cells correlated with several of the metabolic and clinical changes.

Paradoxical Reduction in Pancreatic Glucagon with Normalization of Somatostatin and Decrease in Insulin in Normoglycemic Alloxan-Diabetic Dogs: A Putative Mechanism of Glucagon Irresponsiveness to Hypoglycemia*

“…Morphometric analysis of islets from hyperglycemic diabetic dogs revealed an abundance of immunoreactive glucagon per islet with an increase of 2-3-fold in glucagon area from the control (15-20% to 43-47%). This is in agreement with observations in other species (5)(6)(7)(8)(9)(19)(20)(21). However, the total glucagon content and concentration per pancreas did not change.…”

“…The mean islet size and %IA in dog were close to the value observed in rat and human islets (19,20). Thus, our results are similar to the values that were obtained by the use of point-counting and linear-scanning procedures in other species (5)(6)(7)(8)(9)(19)(20)(21). Diabetes reduced the number of islets and the percent content of islets by 70% in the exocrine pancreas.…”

“…In several animal models of diabetes, low plasma insulin and high plasma glucagon and somatostatin concentrations have been observed (4)(5)(6)(7)(8)(9). In streptozotocindiabetic rats and monkeys, these hormonal alterations were consistent with changes in the content of these hormones and the number of respective cells in the pancreatic islets (5,8).…”

Old World Nonhuman Primate Models of Type 2 Diabetes Mellitus

“…This possibility is evidenced by studies of caloric restriction in monkeys (Cefalu et al 2004) and studies documenting lean elderly people as insulin sensitive as lean youths (Bryhni et al 2003). Islet amyloidosis has been reported in T2DM Macaca mulatta (de Koning et al 1993), Macaca nigra (Howard 1986), Macaca nemestrina (Ohagi et al 1991), Macaca fascicularis (Cromeens and Stephens 1985;O'Brien et al1996), and baboons (Hubbard et al 2002). We reported that the amyloid is immunoreactive for islet amyloid polypeptide (IAPP 1 ) and is generally associated with a marked reduction in insulin-immunoreactive ␤-cells (O'Brien et al 1996;Wagner et al 1996bWagner et al , 2001.…”

“…Diabetes has been reported in a number of Old World NHPs, including many macaque species (e.g., cynomolgus, rhesus, bonnet, Formosan rock, pig-tailed, and celebes macaques), African green monkeys, and baboons (Bodkin 2000;Clarkson et al 1985;Cromeens and Stephens 1985;de Koning et al 1993;Hansen and Bodkin 1986;Howard 1986;O'Brien et al 1996;Ohagi et al 1991;Tigno et al 2004;Wagner et al 1996a,b;Yasuda et al 1988). As in humans, most NHPs with diabetes have T2DM (Wagner et al 1996b(Wagner et al , 2001.…”