Low-Carbohydrate Diet Modulates Glucose-Lipid Utilization in Skeletal Muscle of Diabetic Mice

Nutrients. 2023 Mar 21;15(6):1513. doi: 10.3390/nu15061513.

Abstract

Type 2 diabetes is associated with many complications, including skeletal muscle atrophy. Ketogenic diets and low-carbohydrate diets (LCD) have recently been introduced as dietary interventions in patients with diabetes, but their effects on glucose and lipid metabolism in skeletal muscle have not been studied. In the current study, we compared the effects of LCD and ketogenic diet on glucose and lipid metabolism in skeletal muscle of diabetic mice. C57BL/6J mice with type 2 diabetes, constructed by a high-fat diet combined with streptozotocin, were fed a standard diet, a high-fat diet, an LCD, or a ketogenic diet for 14 weeks, respectively. Here, we found that the LCD, rather than the ketogenic diet, retained skeletal muscle weight and suppressed the expression of atrophy-related genes in diabetic mice. In addition, the LCD had more glycolytic/type IIb myofiber content and inhibited forkhead box O1 and pyruvate dehydrogenase kinase 4 expression, leading to improved glucose utilization. However, the ketogenic diet maintained more oxidative/type I myofibers. Moreover, compared with the ketogenic diet, the LCD decreased intramuscular triglycerides content and muscle lipolysis, suggesting improvement in lipid metabolism. Taken together, these data suggested that the LCD improved glucose utilization, and inhibited lipolysis and atrophy in skeletal muscle of diabetic mice, while the ketogenic diet showed metabolic disorders in skeletal muscle.

Keywords: glucose utilization; ketogenic diet; low-carbohydrate diet; skeletal muscle; type 2 diabetes.

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental* / metabolism
  • Diabetes Mellitus, Type 2*
  • Diet, Carbohydrate-Restricted
  • Diet, High-Fat / adverse effects
  • Diet, Ketogenic*
  • Glucose / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Skeletal / metabolism
  • Triglycerides / metabolism

Substances

  • Glucose
  • Triglycerides
  • Blood Glucose