Intestinal glucose metabolism revisited

Area of Science:

• Endocrinology
• Neuroscience
• Metabolic Research

Background:

• The gut's role in glucose homeostasis is well-established, primarily through glucose utilization.
• Recent research highlights a novel function: intestinal gluconeogenesis, contributing significantly to endogenous glucose production during fasting.

Purpose of the Study:

• To explore the novel function of intestinal gluconeogenesis.
• To elucidate the mechanisms by which intestinal gluconeogenesis communicates with the brain to regulate energy homeostasis, satiety, and glucose metabolism.
• To investigate the involvement of intestinal gluconeogenesis in the effects of dietary components and obesity interventions.

Main Methods:

• Review of recent scientific literature on intestinal gluconeogenesis.
• Analysis of proposed signaling pathways involving the gut-brain axis.
• Examination of the roles of specific receptors like SGLT3 and FFAR3.
• Discussion of the implications for dietary interventions and bariatric surgery.

Main Results:

• Intestinal gluconeogenesis contributes 20-25% to endogenous glucose production during fasting.
• This process initiates a gut-brain communication pathway, influencing hunger and whole-body glucose homeostasis.
• Dietary proteins and soluble fibers stimulate intestinal gluconeogenesis, mediating satiety and exerting anti-obesity/anti-diabetic effects.
• Receptors like SGLT3 and FFAR3 are implicated in sensing glucose and propionate, respectively, to activate this gut-brain reflex.
• Intestinal gluconeogenesis is potentially involved in metabolic improvements following gastric bypass surgery.

Conclusions:

• Intestinal gluconeogenesis represents a critical link between gut function and central regulation of energy and glucose homeostasis.
• This pathway offers potential therapeutic targets for obesity and type 2 diabetes.
• Further research into the gut-brain axis mediated by intestinal gluconeogenesis is warranted.