Dietary modulation of alpha-cell volume and function in strain 129/J mice

Weanling female 129/J mice were maintained for 1, 2, 3, or 6 mo on either a control diet containing 60% sucrose and 23% protein or an isocaloric, high-protein, no-carbohydrate diet containing 83% protein and 0% sucrose. Mice were killed after each interval to assess the effect of diet on histological and physiological changes in the endocrine pancreas. Image analysis of islets stained immunocytochemically for alpha-cells, beta-cells, delta-cells, and PP cells was performed to quantify changes in islet structure. It was found that islet composition was strongly affected by diet. The volume density of the alpha-cells was significantly elevated in mice fed the high-protein diet (e.g., 35% vs. 16% in controls at 6 mo), whereas the volume density of beta-cells concomitantly decreased from 65 to 39%. Radioimmunoassay of the insulin and glucagon content of the pancreas and the plasma corroborated the morphometric findings. Pancreatic and plasma glucagon concentration in mice on the high-protein diet was elevated by an average of 2.5-fold above controls, whereas pancreatic insulin concentration was diminished by nearly half. The increase in alpha-cell volume density and pancreatic glucagon concentration appeared initially due to alpha-cell hypertrophy, although by 6 mo of high-protein feeding both hypertrophy and hyperplasia of the alpha-cells were evident. Presumably, these changes were compensatory responses to the increased functional demand on alpha-cells (i.e., glucagon biosynthesis and secretion) imposed by chronic high-protein feeding.