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

• Published in: European journal of nutrition 2017-02, Vol.56 (1), p.237-246
• Main Authors: Arimura, Emi, Pulong, Wijang Pralampita, Marchianti, Ancah Caesarina Novi, Nakakuma, Miwa, Abe, Masaharu, Ushikai, Miharu, Horiuchi, Masahisa
• Format: Article
• Language: English
• Subjects: Albuminuria - metabolism; Animals; Blood Glucose - metabolism; Body Weight; C-Peptide - urine; Carbohydrate Metabolism; Chemistry; Chemistry and Materials Science; Diabetes Mellitus, Experimental - physiopathology; Diabetes Mellitus, Type 2 - physiopathology; Diet, Carbohydrate-Restricted; Dietary Carbohydrates - administration & dosage; Dietary Proteins - administration & dosage; Dietary Proteins - analysis; Insulin - blood; Insulin - metabolism; Insulin Secretion; Leptin - blood; Male; Maltose - administration & dosage; Mice; Mice, Inbred C57BL; Mice, Knockout; Nutrition; Original Contribution; Starch - administration & dosage
• ISSN: 1436-6207; 1436-6215; 1435-1293
• DOI: 10.1007/s00394-015-1075-y

Purpose 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. Methods 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 15 days. 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. Results 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 30 min than db–H mixture mice. However, db mice administered starch–H mixture showed significantly higher blood glucose 120–300 min post-administration than db–L mixture mice, although both groups exhibited similar insulin levels. Conclusions 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.