Title:Physiological Mechanisms of Action of Incretin and Insulin in Regulating Skeletal Muscle Metabolism
Volume: 10
Issue: 5
Author(s): Haitham Abdulla, Bethan Phillips, Kenneth Smith, Daniel Wilkinson, Philip J. Atherton and Iskandar Idris
Affiliation:
Keywords:
Glucagon like peptide-1, insulin, diabetes, skeletal muscle metabolism, microvascular recruitment, microvascular
blood flow.
Abstract: Type II diabetes (T2D) is a progressive condition affecting approximately 350 million adults worldwide.
Whilst skeletal muscle insulin resistance and beta-cell dysfunction are recognised causes of T2D, progressive loss of lean
muscle mass (reducing surface area for glucose disposal area) in tandem with ageing-related adiposity (i.e. sarcopenic
obesity) also plays an important role in driving hyperglycaemia progression. The anabolic effects of nutrition on the muscle
are driven by the uptake of amino acids, into skeletal muscle protein, and insulin plays a crucial role in regulating this.
Meanwhile glucagon-like peptide (GLP-1) and glucose- dependent insulinotropic peptide (GIP) are incretin hormones released
from the gut into the bloodstream in response to macronutrients, and have an established role in enhancing insulin
secretion. Intriguingly, endocrine functions of incretins were recently shown to extend beyond classical insulinotropic effects,
with GLP-1/GIP receptors being found in extra-pancreatic cells i.e., skeletal muscle and peripheral (muscle) microvasculature.
Since, incretins have been shown to modulate blood flow and muscle glucose uptake in an insulinindependent
manner, incretins may play a role in regulating nutrient-mediated modulation of muscle metabolism and microvascular
tone, independently of their insulinotropic effects. In this review we will discuss the role of skeletal muscle in
glucose homeostasis, disturbances related to insulin resistance, regulation of skeletal muscle metabolism, muscle microvascular
abnormalities and disturbances of protein (PRO) metabolism seen in old age and T2D. We will also discuss
the emerging non-insulinotropic role of GLP-1in modulating skeletal muscle metabolism and microvascular blood flow.
