Insulin sensitivity of protein and glucose metabolism in human forearm skeletal muscle.

Abstract

IntroductionPhysiologic increases of insulin promote net amino acid uptake and protein anabolism in forearm skeletal muscle by restraining protein degradation. The sensitivity of this process to insulin is not known. Using the forearm perfusion method, we infused insulin locally in the brachial artery at rates of 0.00 (saline control), 0.01, 0.02, 0.035, or 0.05 mU/min per kg for 150 min to increase local forearm plasma insulin concentration by 0, -20, -35, -60, and -120 ,U/ml (n = 35). L-Iring-2,6-3Hjphenylalanine and L-11-14Cjleucine were infused systemically, and the net forearm balance, rate of appearance (R.) and rate of disposal (Rd) of phenylalanine and leucine, and forearm glucose balance were measured basally and in response to insulin infusion. Compared to saline, increasing rates of insulin infusion progressively increased net forearm glucose uptake from 0.9 Mmol/min per 100 ml (saline) to 1.0, 1.8, 2.4, and 4.7 ,umol/min per 100 ml forearm, respectively. Net forearm balance for phenylalanine and leucine was significantly less negative than basal (P < 0.01 for each) in response to the lowest dose insulin infusion, 0.01 mU/min per kg, and all higher rates of insulin infusion. The effects ofhyperinsulinemia on skeletal muscle, the largest pool of protein in the body, has been of particular interest. Pozefsky et al. (9), using the forearm perfusion technique, observed that local hyperinsulinemia diminished net forearm amino acid release and stimulated glucose uptake. With direct infusion of insulin into the brachial artery, the effects of hyperinsulinemia on forearm skeletal muscle metabolism can be examined directly (9-13) without the confounding influence of altered substrate concentrations that accompany systemic insulin administration (14,15

Effects of recombinant human growth hormone on muscle protein turnover in malnourished hemodialysis patients.

“…The changes induced by the administration of rhGH were reversed by rhGH discontinuation. Baseline rates of appearance and disposal of phenylalanine measured in this group of malnourished patients are about 30% lower than those measured in well nourished CRF patients under unrestricted diets (4,29) and are also in the lower range of the values recorded in normal subjects in the literature (23,30) and in our laboratory (4). This observation suggests that low rates of protein synthesis occur in the muscle of malnourished HD patients and is in accordance with studies showing a decrease in RNA/DNA ratio in muscle in such patients (31).…”

Role of insulin in the regulation of human skeletal muscle protein synthesis and breakdown: a systematic review and meta-analysis

“…Meta-analysis of study characteristics A total of 13 articles [16,[19][20][21][24][25][26][27][28][29][30][31][32], containing 25 experimental studies using different insulin concentrations, were identified for inclusion in the meta-analysis (Table 1); all analysed the effect of insulin on both MPS and MPB (Table 1). A total of 173 individuals were included in these studies.…”

“…The role of insulin in adult human skeletal muscle is more complex and subject to interplay between other factors such as AA availability, muscle blood flow and microvascular recruitment [16,17]. This has led to various studies reporting opposing conclusions when it comes to the relationship between insulin and human skeletal muscle protein turnover [16][17][18][19][20][21][22]. We therefore undertook a systematic review and meta-analysis in an attempt to clarify the role of insulin in regulating muscle metabolism in humans.…”

Regulation of Muscle Protein Degradation

“…The cellular signaling mechanisms that activate both apoptotic and the Ub-P'some pathways to cause loss of muscle protein remain obscure. One potential mechanism involves insulin/IGF-1 signaling pathways because the predominant effect of insulin on protein turnover in humans is to reduce protein degradation (8). Moreover, insulin resistance is common to metabolic acidosis, uremia, and other catabolic conditions that are associated with activation of the Ub-P'some system (9 -11).…”