Effect of Human Myotubes-Derived Media on Glucose-Stimulated Insulin Secretion

Abstract

Fasting to postprandial transition requires a tight adjustment of insulin secretion to its demand, so tissue (e.g., skeletal muscle) glucose supply is assured while hypo-/hyperglycemia are prevented. High muscle glucose disposal after meals is pivotal for adapting to increased glycemia and might drive insulin secretion through muscle-released factors (e.g., myokines). We hypothesized that insulin influences myokine secretion and then increases glucose-stimulated insulin secretion (GSIS). In conditioned media from human myotubes incubated with/without insulin (100 nmol/L) for 24 h, myokines were qualitatively and quantitatively characterized using an antibody-based array and ELISA-based technology, respectively. C57BL6/J mice islets and Wistar rat beta cells were incubated for 24 h with control and conditioned media from noninsulin- and insulin-treated myotubes prior to GSIS determination. Conditioned media from insulin-treated versus nontreated myotubes had higher RANTES but lower IL6, IL8, and MCP1 concentration. Qualitative analyses revealed that conditioned media from noninsulin- and insulin-treated myotubes expressed 32 and 23 out of 80 myokines, respectively. Islets incubated with conditioned media from noninsulin-treated myotubes had higher GSIS versus control islets (p < 0.05). Meanwhile, conditioned media from insulin-treated myotubes did not influence GSIS. In beta cells, GSIS was similar across conditions. In conclusion, factors being present in noninsulin-stimulated muscle cell-derived media appear to influence GSIS in mice islets.

Myokine Regulation of Insulin Secretion: Impact of Inflammation and Type 2 Diabetes

“…Yet, others have found no effects of physiologic levels of IL6 on insulin secretion . Other exercise-induced factors that have been suggested to improve β-cell mass and/or function include irisin (Natalicchio et al, 2017), RANTES (Mizgier et al, 2017) and Fractalkine (CX3CL1) ( .…”

“…A number of muscle-derived factors have been shown to modulate GSIS: irisin (Natalicchio et al, 2017), IL6 (Ellingsgaard et al, 2011;Christensen et al, 2015), fractalkine , angiogenin, and osteoprotegerin (Rutti et al, 2018) and Wnt3a (Kozinski et al, 2016); RANTES improved basal insulin secretion, but was without effect on GSIS (Mizgier et al, 2017). The involvement of any of these factors in the responses described in the current report might be questioned, as many of these same factors also protected the β-cell or islet systems studied from apoptosis, while we found no such effects of specific MT-CM on caspase 3 cleavage, an accepted marker of apoptosis.…”

“…The involvement of any of these factors in the responses described in the current report might be questioned, as many of these same factors also protected the β-cell or islet systems studied from apoptosis, while we found no such effects of specific MT-CM on caspase 3 cleavage, an accepted marker of apoptosis. However, comparisons between studies are complicated by the use of different challenges for muscle cells; palmitate alone (Natalicchio et al, 2017), insulin alone (Mizgier et al, 2017), or selected cytokines (Christensen et al, 2015;Rutti et al, 2015Rutti et al, , 2018. Also, none of these studies evaluated MT from individuals with T2D.…”

Exercise-Released Myokines in the Control of Energy Metabolism

“…We recently observed a significant increase in glucose-stimulated insulin secretion from isolated mice islets in response to conditioned media from resting non-treated human primary myotubes. This indicates that skeletal muscle cells produces basal rates of secreted factors capable of modulating insulin secretion (Mizgier et al, 2017).…”

Insights on the Role of Putative Muscle-Derived Factors on Pancreatic Beta Cell Function

“…Muscle cell adaptation also involves autocrine and paracrine interaction among cell types (Pillon et al, 2013). Thus, several muscle cell-derived factors have been detected, including myokines (Bouzakri et al, 2011; Raschke et al, 2013; Scheler et al, 2013; Hartwig et al, 2014; Mizgier et al, 2017), exosomes and their cargo (Forterre et al, 2014), and metabolites (Daskalaki et al, 2018). Whether or not muscle-derived factors increase in blood at a sufficient magnitude to influence distant organs has not yet been elucidated.…”