American journal of physiology. Endocrinology and metabolism
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Am. J. Physiol. Endocrinol. Metab. · Jan 2018
Cholesterol metabolism and Cx43, Cx46, and Cx50 gap junction protein expression and localization in normal and diabetic and obese ob/ob and db/db mouse testes.
Decreased fertility and birth rates arise from metabolic disorders. This study assesses cholesterol metabolism and Cx46, Cx50, and Cx43 expression in interstitium- and seminiferous tubule-enriched fractions of leptin-deficient ( ob/ob) and leptin receptor-deficient ( db/db) mice, two type 2 diabetes and obesity models associated with infertility. Testosterone levels decreased and glucose and free and esterified cholesterol (FC and EC) levels increased in serum, whereas FC and EC levels decreased in the interstitium, in ob/ob and db/db mice. ⋯ Apoptosis levels measured by ELISA and numbers of apostain-labeled apoptotic cells significantly increased in db/db, but not ob/ob, tubules. Testicular db/db capillaries were Cx50-positive but weakly Cx43-positive with a thickened lamina, suggesting altered permeability. Our findings indicate that the db mutation-induced impairment of meiosis may arise from imbalances in cholesterol metabolism and upregulated Cx43 expression and phosphorylation in tubules.
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Am. J. Physiol. Endocrinol. Metab. · Nov 2016
ReviewDoes the muscle protein synthetic response to exercise and amino acid-based nutrition diminish with advancing age? A systematic review.
The precise role of age-related muscle anabolic resistance in the progression of sarcopenia and functional decline in older individuals is unclear. The present aim was to assess whether the muscle protein synthesis (MPS) response to acute exercise (endurance or resistance) and/or amino acid-based nutrition is attenuated in older compared with young individuals. A systematic review was conducted on studies that directly examined the influence of age on the MPS response to exercise and/or amino acid-based nutrition. ⋯ When exercise and amino acid-based nutrition were combined, only 2 of the 10 study arms provided sufficient evidence of age-related muscle anabolic resistance. Our results highlight that optimization of exercise and amino acid-based nutrition is sufficient to induce a comparable MPS response between young and older individuals. However, the exercise volume completed and/or the amino acid/protein dose and leucine content must exceed a certain threshold to stimulate equivalent MPS rates in young and older adults, below which age-related muscle anabolic resistance may become apparent.
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Am. J. Physiol. Endocrinol. Metab. · Nov 2015
Nε-(carboxymethyl) lysine-induced mitochondrial fission and mitophagy cause decreased insulin secretion from β-cells.
Nε-(carboxymethyl) lysine-conjugated bovine serum albumin (CML-BSA) is a major component of advanced glycation end products (AGEs). We hypothesised that AGEs reduce insulin secretion from pancreatic β-cells by damaging mitochondrial functions and inducing mitophagy. Mitochondrial morphology and the occurrence of autophagy were examined in pancreatic islets of diabetic db/db mice and in the cultured CML-BSA-treated insulinoma cell line RIN-m5F. ⋯ Additionally, increased levels of Parkin and PTEN-induced putative kinase 1 protein suggest that fragmented mitochondria were associated with increased mitophagic activity, and ALA attenuated the CML-BSA-induced mitophage formation. Our study demonstrated that CML-BSA induced mitochondrial dysfunction and mitophagy in pancreatic β-cells. The findings from this study suggest that increased concentration of AGEs may damage β-cells and reduce insulin secretion.
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Am. J. Physiol. Endocrinol. Metab. · Oct 2015
Involvement of AMPK in regulating slow-twitch muscle atrophy during hindlimb unloading in mice.
AMPK is considered to have a role in regulating skeletal muscle mass. However, there are no studies investigating the function of AMPK in modulating skeletal muscle mass during atrophic conditions. In the present study, we investigated the difference in unloading-associated muscle atrophy and molecular functions in response to 2-wk hindlimb suspension between transgenic mice overexpressing the dominant-negative mutant of AMPK (AMPK-DN) and their wild-type (WT) littermates. ⋯ The expressions of ubiquitinated proteins and muscle RING finger 1 mRNA and protein, markers of the ubiquitin-proteasome system, were increased by hindlimb unloading in WT mice but not in AMPK-DN mice. The expressions of molecules related to the protein degradation system, phosphorylated forkhead box class O3a, inhibitor of κBα, microRNA (miR)-1, and miR-23a, were decreased only in WT mice in response to hindlimb unloading, and 72-kDa heat shock protein expression was higher in AMPK-DN mice than in WT mice. These results imply that AMPK partially regulates unloading-induced atrophy of slow-twitch muscle possibly through modulation of the protein degradation system, especially the ubiquitin-proteasome system.
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Am. J. Physiol. Endocrinol. Metab. · Aug 2015
Multicenter StudyMitochondrial respiratory capacity and coupling control decline with age in human skeletal muscle.
Mitochondrial health is critical to physiological function, particularly in tissues with high ATP turnover, such as striated muscle. It has been postulated that derangements in skeletal muscle mitochondrial function contribute to impaired physical function in older adults. Here, we determined mitochondrial respiratory capacity and coupling control in skeletal muscle biopsies obtained from young and older adults. ⋯ Calculation of respiratory function revealed lower respiration linked to ATP production (P < 0.001) and greater reserve respiration (P < 0.01); i.e., respiratory capacity not used for phosphorylation in muscle from older adults. We conclude that skeletal muscle mitochondrial respiratory capacity and coupling control decline with age. Lower respiratory capacity and coupling efficiency result in a reduced capacity for ATP production in skeletal muscle of older adults.