Abstract

In type-2 diabetes, both insufficient insulin and excessive glucagon secretion contribute to hyperglycemia. We compared insulin, glucagon and somatostatin stores in pancreas obtained at autopsy of 20 lean and 19 obese non-diabetic (ND), and 18 type-2 diabetic (T2D) subjects. From concentrations and pancreas weight, total content of hormones was calculated. Insulin content was 35% lower in T2D than ND subjects (7.4 versus 11.3 mg), whereas glucagon content was similar (0.76 versus 0.81 mg). The higher ratio of glucagon/insulin contents in T2D was thus explained by the decrease in insulin. With increasing BMI of ND subjects, insulin and glucagon contents respectively tended to increase and decrease, resulting in a lower glucagon/insulin ratio in obesity. With aging, insulin and glucagon contents did not significantly change in ND subjects but declined in T2D subjects, without association with the duration of diabetes or type of treatment. The somatostatin content was lower in T2D than ND subjects (0.027 versus 0.038 mg), but ratios somatostatin/insulin and somatostatin/glucagon were not different. In conclusion, insulin stores are about 1/3 lower in T2D than ND subjects, whereas glucagon stores are unchanged. Abnormal secretion of each hormone in type-2 diabetes cannot be attributed to major alterations in their pancreatic reserves.

Highlights

  • Glucose homeostasis mainly relies on the opposite hypoglycemic and hyperglycemic properties of insulin and glucagon

  • We report measurements of insulin, glucagon and somatostatin in the pancreas of 18 type-2 diabetic (T2D) subjects and 39 ND subjects

  • In the group of 39 ND subjects the insulin content averaged 11.3 ± 3.9 mg and it was 35% lower in T2D subjects (7.4 ± 3.9 mg, P < 0.005)

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Summary

Introduction

Glucose homeostasis mainly relies on the opposite hypoglycemic and hyperglycemic properties of insulin and glucagon. In type-2 diabetic (T2D) subjects, hyperglycemia is largely the consequence of insufficient insulin secretion and excessive glucagon secretion in a context of insulin resistance[1,2,3]. These secretory abnormalities may result from isolated or combined alterations in the function and number of pancreatic β- and α-cells. We report measurements of insulin, glucagon and somatostatin in the pancreas of 18 T2D subjects and 39 ND subjects The number of the latter permitted assessment of the impact of obesity by comparing 20 lean non-diabetic subjects (LND) and 19 obese non-diabetic subjects (OND)

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