Mechanisms by which a Very-Low-Calorie Diet Reverses Hyperglycemia in a Rat Model of Type 2 Diabetes

Abstract

Caloric restriction rapidly reverses type 2 diabetes (T2D), but the mechanism(s) of this reversal are poorly understood. Here we show that 3 days of a very-low-calorie diet (VLCD, one-quarter their typical intake) lowered plasma glucose and insulin concentrations in a rat model of T2D without altering body weight. The lower plasma glucose was associated with a 30% reduction in hepatic glucose production resulting from suppression of both gluconeogenesis from pyruvate carboxylase (V), explained by a reduction in hepatic acetyl-CoA content, and net hepatic glycogenolysis. In addition, VLCD resulted in reductions in hepatic triglyceride and diacylglycerol content and PKCɛ translocation, associated with improved hepatic insulin sensitivity. Taken together, these data show that there are pleotropic mechanisms by which VLCD reverses hyperglycemia in a rat model of T2D, including reduced DAG-PKCɛ-induced hepatic insulin resistance, reduced hepatic glycogenolysis, and reduced hepatic acetyl-CoA content, PC flux, and gluconeogenesis.

Insulin resistance is improved in high‐fat fed mice by photobiomodulation therapy at 630 nm

“…Many pharmacological and non‐pharmacological interventions such as physical exercise , caloric restriction and use of medications such as metformin are known to reverse or attenuate obesity‐related insulin resistance. However, another non‐pharmacological strategy that has recently been shown to improve obesity‐induced dysfunctions is photobiomodulation therapy (PBMT).…”

Metabolic surgery for the treatment of type 2 diabetes in patients with BMI lower than 35 kg/m2: Why caution is still needed

“…Nonresponders had strikingly more intrapancreatic fat than responders before and after the 8‐week period. Potential mechanisms of acute caloric restriction leading to decreased hepatic insulin resistance have also been postulated in a recent study and include a reduction in intrahepatic glycogenolysis and acetyl‐CoA‐driven pyruvate carboxylase flux . Several studies argue that caloric restriction would be a useful strategy for acute diabetes improvement and even remission, particularly in patients recently diagnosed with diabetes, since beta‐cell failure and transdifferentiation occurs as the disease progresses to a point in which other measures to achieve normoglycemia would be necessary …”

“…Potential mechanisms of acute caloric restriction leading to decreased hepatic insulin resistance have also been postulated in a recent study and include a reduction in intrahepatic glycogenolysis and acetyl-CoAdriven pyruvate carboxylase flux. 66 Several studies argue that caloric restriction would be a useful strategy for acute diabetes improvement and even remission, particularly in patients recently diagnosed with diabetes, since beta-cell failure and transdifferentiation occurs as the disease progresses to a point in which other measures to achieve normoglycemia would be necessary. 39,67,68 The recently published DiRECT study has demonstrated that this analysis could be replicated in a real-life primary care setting by targeting only patients with diabetes diagnosed in the previous 6 years.…”

A review of the molecular pathways mediating the improvement in diabetes mellitus following caloric restriction

“…CR was prescribed by ancient physicians as a therapeutic strategy for the treatment of T2DM (Schäfer, 2005). Recent studies have shown that CR reduces blood glucose through several molecular pathways that modulate insulin sensitivity in peripheral tissues and these are reviewed here (Perry et al, 2018). (Hauner, 2017;Verma & Hussain, 2017).…”