Poster Presentation 4th Metabolic Diseases; Breakthrough Discoveries in Diabetes & Obesity Meeting 2024

Nutrient specific modulation of insulin action and skeletal muscle signalling pathways (#186)

Vicky Kuriel 1 , Benjamin L Parker 2 , Giang Dao 1 , Tim Connor 1 , Conor J Kelly 3 , Minnie Seward 3 , Kirsten F Howlett 1 , Greg M Kowalski 1 , Clinton R Bruce 1 , Chris S Shaw 1
  1. Institute for Physical Activity and Nutrition, Deakin University, Waurn Ponds, VIC, Australia
  2. Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC, Australia
  3. University Hospital Geelong, Barwon Health, Geelong, VIC, Australia

Ingestion of glucose or protein in isolation stimulate insulin secretion yet elicit divergent responses on glucose disposal (Rd). Here, we aimed to determine if nutrient-specific effects on muscle insulin signalling underlie the divergent effects on glucose disposal elicited by glucose and protein ingestion.

Participants (6 females/5 males, 26±7 years, BMI: 24.7±2.5 kg/m2) completed 2 separate trials, involving ingestion of 25 g glucose or 25 g whey protein (designed to be isocalorically matched and to elicit a similar insulin response) in random order. In the glucose trial, the triple tracer technique was used to assess postprandial glucose flux. Participants consumed 25 g glucose containing [1-2H]glucose (4%) while [U13C]glucose and [6,6-2H]glucose were infused at variable rates over a 3h period. In the protein trial, [6,6-2H]glucose was infused at a constant rate for 3h. Muscle biopsies were collected from the vastus lateralis at baseline and at 30 min and 60 min post-feeding.

While the postprandial insulin response was matched between trials, plasma glucose levels were higher after glucose ingestion. Despite similar insulin responses, divergent effects on Rd were observed. Rd was elevated ~4-fold above baseline in the glucose trial, yet only increased by ~20% with protein ingestion. Endogenous glucose production (EGP) was suppressed following glucose ingestion, while it progressively increased after protein ingestion, peaking ~20% above basal.  Plasma FFA and glycerol were similarly suppressed in both trials, suggesting equal suppression of adipose tissue lipolysis. Despite similar insulin responses, phosphoproteomic analysis revealed major divergence in the muscle signalling between glucose and protein ingestion.

These data highlight a disconnect between postprandial hyperinsulinemia and stimulation of Rd, which is dependent on the nutrient stimulus for insulin secretion. Interestingly, there was no divergence in the suppression of adipose tissue lipolysis, with both protein and glucose suppressing FFA and glycerol equally.