Abstract
It has become increasingly apparent that substrate metabolism is subject to gender-specific regulation, and the aim of this review is to outline the available evidence of molecular gender differences in glucose and lipid metabolism of skeletal muscle. Female sex has been suggested to have a favorable effect on glucose homeostasis, and the available evidence from hyperinsulinemic–euglycemic clamp studies is summarized to delineate whether there is a gender difference in whole-body insulin sensitivity and in particular insulin-stimulated glucose uptake of skeletal muscle. Whether an eventual higher insulin sensitivity of female skeletal muscle can be related to gender-specific regulation of molecular metabolism will be topic for discussion. Gender differences in muscle fiber type distribution and substrate availability to and in skeletal muscle are highly relevant for substrate metabolism in men and women. In particular, the molecular machinery for glucose and fatty acid oxidative and storage capacities in skeletal muscle and its implications for substrate utilization during metabolic situations of daily living are discussed, emphasizing their relevance for substrate choice in the fed and fasted state, and during periods of physical activity and recovery. Together, handling of carbohydrate and lipids and regulation of their utilization in skeletal muscle have implications for whole-body glucose homeostasis in men and women. 17-β estradiol is the most important female sex hormone, and the identification of estradiol receptors in skeletal muscle has opened for a role in regulation of substrate metabolism. Also, higher levels of circulating adipokines as adiponectin and leptin in women and their implications for muscle metabolism will be considered.
Highlights
The number of diagnosed type 2 diabetic (T2D) patients is still increasing, and notably the global prevalence is reported to be higher in men than women [1]
A higher basal as well as insulin-stimulated methyl-glucose uptake was observed in vitro in female versus male subcutaneous adipocytes, when expressed www.frontiersin.org per cell number [51]. These findings opens for a particular significant role of adipose tissue in whole-body glucose uptake in women, and it follows that gender differences in glucose uptake and metabolism of adipose tissue in vivo await further comparative studies
We have reported 160% higher mRNA of muscle lipoprotein lipase (mLPL) in young women compared to matched males [92], and in support of this a 160% higher mLPL mRNA was reported in skeletal muscle from 40 to 65 years old obese women compared to men [93]
Summary
The number of diagnosed type 2 diabetic (T2D) patients is still increasing, and notably the global prevalence is reported to be higher in men than women [1]. Matching of men and women in regard to body composition, maximal oxygen uptake (VO2-peak) per lean body mass (LBM), training status, and menstrual cyclicity is crucial in order to determine the effect of sex per se. Skeletal muscle has been described as a quantitatively important site for insulin-stimulated glucose clearance, in studies evaluating peripheral glucose disposal by the leg arterio-venous (a-v) balance technique [2]. This implicates the importance of investigating possible sex differences in insulin action in muscle. Clinical trials conducted by our research group contribute with important information, measuring glucose uptake across the leg by applying the femoral a-v balance technique on carefully matched men and women.
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