Insulin resistance in health and disease: exploring the role of disuse skeletal muscle atrophy, testosterone and Beta-Hydroxy-Beta-Methylbutyrate (HMB) in young and older men

Background Combined exercise and nutraceutical interventions seems to have the potential to reverse some of the catabolic state associated with human skeletal muscle disuse atrophy and to positively influence glucose metabolism, however mechanisms underlying these processes are poorly defined and needs further exploration. Methods This thesis carried out a literature review of human skeletal muscle disuse atrophy and the effects on glucose metabolism before describing 3 randomised controlled trials to evaluate the effect of single leg immobilisation on muscle disuse in young men, effects of testosterone suppression (young men) and supplementation (old men) in addition to resistance exercise on glycaemic control and the role of Beta-Hydroxy-Beta-Methylbutyrate (HMB) supplementation on glucose metabolism in young and old men. Results Literature review revealed that immobilisation lowers fasted state muscle protein synthesis (MPS) and induces fed-state ‘anabolic resistance’ and induces muscle insulin resistance (IR). The randomised controlled trial described in this thesis showed that disuse atrophy acutely is driven by decline in MPS rather than increase in muscle protein breakdown (MPB) and seems to induce insulin resistance. Further, Testosterone (T) therapy and non-suppressed endogenous T, enhanced insulin sensitivity in older and young men, respectively, coupled with RET. Finally, HMB significantly reduced the insulin area-under-the-curve (AUC) with no difference in glucose AUC, resulting in a trend towards an increase in the Cederholm index of insulin sensitivity in younger men. Conclusions A multitudinous approach may be needed to overcome the increasing burden of persistent IR states such as Type 2 diabetes associated with loss of skeletal muscle: sarcopenia (disuse, disease, ageing etc.) and anabolic hormone resistance (ageing). So, our study tries to approach this complex area and it may be conceivable to address this issue by combining pre/re-habilitation (combined with RET) post muscle disuse, combined with anabolic hormone replacement (testosterone) and with nutraceuticals (HMB) supplementation

Insulin resistance in health and disease: exploring the role of disuse skeletal muscle atrophy, testosterone and Beta-Hydroxy-Beta-Methylbutyrate (HMB) in young and older men

Background Combined exercise and nutraceutical interventions seems to have the potential to reverse some of the catabolic state associated with human skeletal muscle disuse atrophy and to positively influence glucose metabolism, however mechanisms underlying these processes are poorly defined and needs further exploration. Methods This thesis carried out a literature review of human skeletal muscle disuse atrophy and the effects on glucose metabolism before describing 3 randomised controlled trials to evaluate the effect of single leg immobilisation on muscle disuse in young men, effects of testosterone suppression (young men) and supplementation (old men) in addition to resistance exercise on glycaemic control and the role of Beta-Hydroxy-Beta-Methylbutyrate (HMB) supplementation on glucose metabolism in young and old men. Results Literature review revealed that immobilisation lowers fasted state muscle protein synthesis (MPS) and induces fed-state ‘anabolic resistance’ and induces muscle insulin resistance (IR). The randomised controlled trial described in this thesis showed that disuse atrophy acutely is driven by decline in MPS rather than increase in muscle protein breakdown (MPB) and seems to induce insulin resistance. Further, Testosterone (T) therapy and non-suppressed endogenous T, enhanced insulin sensitivity in older and young men, respectively, coupled with RET. Finally, HMB significantly reduced the insulin area-under-the-curve (AUC) with no difference in glucose AUC, resulting in a trend towards an increase in the Cederholm index of insulin sensitivity in younger men. Conclusions A multitudinous approach may be needed to overcome the increasing burden of persistent IR states such as Type 2 diabetes associated with loss of skeletal muscle: sarcopenia (disuse, disease, ageing etc.) and anabolic hormone resistance (ageing). So, our study tries to approach this complex area and it may be conceivable to address this issue by combining pre/re-habilitation (combined with RET) post muscle disuse, combined with anabolic hormone replacement (testosterone) and with nutraceuticals (HMB) supplementation

Synthesis and pharmacological activity of 2H-3-(various substituted indol-2'-carboxamidyl)-3,4-dihydro-1,3-benzoxazines and 2H-3-(2',5'-disubstituted indol-3'-yl)methyl-1,3-benzoxazoles

453-46

Homeostatic regulation of the endoneurial microenvironment during development, aging and in response to trauma, disease and toxic insult

The endoneurial microenvironment, delimited by the endothelium of endoneurial vessels and a multi-layered ensheathing perineurium, is a specialized milieu intérieur within which axons, associated Schwann cells and other resident cells of peripheral nerves function. The endothelium and perineurium restricts as well as regulates exchange of material between the endoneurial microenvironment and the surrounding extracellular space and thus is more appropriately described as a blood–nerve interface (BNI) rather than a blood–nerve barrier (BNB). Input to and output from the endoneurial microenvironment occurs via blood–nerve exchange and convective endoneurial fluid flow driven by a proximo-distal hydrostatic pressure gradient. The independent regulation of the endothelial and perineurial components of the BNI during development, aging and in response to trauma is consistent with homeostatic regulation of the endoneurial microenvironment. Pathophysiological alterations of the endoneurium in experimental allergic neuritis (EAN), and diabetic and lead neuropathy are considered to be perturbations of endoneurial homeostasis. The interactions of Schwann cells, axons, macrophages, and mast cells via cell–cell and cell–matrix signaling regulate the permeability of this interface. A greater knowledge of the dynamic nature of tight junctions and the factors that induce and/or modulate these key elements of the BNI will increase our understanding of peripheral nerve disorders as well as stimulate the development of therapeutic strategies to treat these disorders