Postprandial microvascular blood flow in skeletal muscle: Similarities and disparities to the hyperinsulinaemic‐euglycaemic clamp

Abstract

Skeletal muscle contributes to ~40% of total body mass and has numerous important mechanical and metabolic roles in the body. Skeletal muscle is a major site for glucose disposal following a meal. Consequently, skeletal muscle plays an important role in postprandial blood glucose homeostasis. Over the past number of decades, research has demonstrated that insulin has an important role in vasodilating the vasculature in skeletal muscle in response to an insulin infusion (hyperinsulinaemic‐euglycaemic clamp) or following the ingestion of a meal. This vascular action of insulin is pivotal for glucose disposal in skeletal muscle, as insulin‐stimulated vasodilation increases the delivery of both glucose and insulin to the myocyte. Notably, in insulin‐resistant states such as obesity and type 2 diabetes, this vascular response of insulin in skeletal muscle is significantly impaired. Whereas the majority of work in this field has focussed on the action of insulin alone on skeletal muscle microvascular blood flow and myocyte glucose metabolism, there is less understanding of how the consumption of a meal may affect skeletal muscle blood flow. This is in part due to complex variations in glucose and insulin dynamics that occurs postprandially—with changes in humoral concentrations of glucose, insulin, amino acids, gut and pancreatic peptides—compared to the hyperinsulinaemic‐euglycaemic clamp. This review will address the emerging body of evidence to suggest that postprandial blood flow responses in skeletal muscle may be a function of the nutritional composition of a meal.

Impaired postprandial skeletal muscle vascular responses to a mixed meal challenge in normoglycaemic people with a parent with type 2 diabetes

“…Lambadiari et al demonstrated that the macrovascular impairment influenced postprandial glucose disposal (with forearm muscle blood flow positively correlating with muscle glucose disposal) [24]. However, that study did not assess skeletal muscle specific MBF which is important because it is the microvasculature that controls glucose and insulin delivery to the myocyte [20,25,33,34] because not all vasodilators that augment large artery blood flow concomitantly increase glucose disposal to muscle. Methacholine and sodium nitroprusside can each increase large artery blood flow but can have opposing effects on muscle insulin-mediated glucose disposal [35,36].…”

“…Skeletal muscle glucose uptake and utilisation occur via a combination of an increase in blood glucose concentration (mass action effect), and a rise in endogenous insulin levels enhancing glucose uptake into tissues from the bloodstream [8]. Regulation of muscle blood flow by insulin is an important physiological process as it controls the rate of glucose and insulin delivery to the myocyte [20,21]. In skeletal muscle of healthy people, physiological hyperinsulinaemia, either during a hyperinsulinaemiceuglycaemic clamp or elicited via mixed meal ingestion, stimulates both total-limb blood flow (macrovascular blood flow) and MBF [10][11][12].…”

High-glucose mixed-nutrient meal ingestion impairs skeletal muscle microvascular blood flow in healthy young men

“…Although intravenous glucose infusion leads to impaired limb arterial blood flow in healthy individuals (10), glucose levels were clamped to a much higher level (15 mmol/L sustained over 2 h) than that observed in the current study (~7.4 mmol/L peak). It is also possible that the intravenous nature of glucose and insulin infusion, bypassing the gut and subsequent release of many gut-derived hormones, is likely to elicit considerably different hemodynamic responses from that of oral macronutrient ingestion (38,42). For example, a 2-h intravenous hyperglycemic clamp (15 mmol/L) in healthy individuals leads to increased systolic and diastolic blood pressure and decreased leg arterial blood flow (10,27).…”

Prior exercise enhances skeletal muscle microvascular blood flow and mitigates microvascular flow impairments induced by a high‐glucose mixed meal in healthy young men

“…This is important, as the exogenous and endogenous glycaemic and hormonal responses elicited by orally ingested nutrients and intravenous insulin and glucose infusion are markedly different (Mingrone et al 2020). Therefore, the microvascular responses are likely to vary when comparing intravenous infusions and orally ingested nutrients (Roberts-Thomson et al 2020).…”

“…Therefore, the microvascular responses are likely to vary when comparing intravenous infusions and orally ingested nutrients (Roberts‐Thomson et al . 2020).…”