Deteriorated glucose metabolism with a high-protein, low-carbohydrate diet in db mice, an animal model of type 2 diabetes, might be caused by insufficient insulin secretion.

Abstract

We previously showed the deleterious effects of increased dietary protein on renal manifestations and glucose metabolism in leptin receptor-deficient (db) mice. Here, we further examined its effects on glucose metabolism, including urinary C-peptide. We also orally administered mixtures corresponding to low- or high-protein diets to diabetic mice. In diet experiments, under pair-feeding (equivalent energy and fat) conditions using a metabolic cage, mice were fed diets with different protein content (L diet: 12% protein, 71% carbohydrate, 17% fat; H diet: 24% protein, 59% carbohydrate, 17% fat) for 15days. In oral administration experiments, the respective mixtures (L mixture: 12% proline, 71% maltose or starch, 17% linoleic acid; H mixture: 24% proline, 59% maltose or starch, 17% linoleic acid) were supplied to mice. Biochemical parameters related to glucose metabolism were measured. The db-H diet mice showed significantly higher water intake, urinary volume, and glucose levels than db-L diet mice but similar levels of excreted urinary C-peptide. In contrast, control-H diet mice showed significantly higher C-peptide excretion than control-L diet mice. Both types of mice fed H diet excreted high levels of urinary albumin. When maltose mixtures were administered, db-L mixture mice showed significantly higher blood glucose after 30min than db-H mixture mice. However, db mice administered starch-H mixture showed significantly higher blood glucose 120-300min post-administration than db-L mixture mice, although both groups exhibited similar insulin levels. High-protein, low-carbohydrate diets deteriorated diabetic conditions and were associated with insufficient insulin secretion in db mice. Our findings may have implications for dietary management of diabetic symptoms in human patients.