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

Abstract

Skeletal muscle (SkM) secretes protein factors (myokines) that can exert multiple actions. To study the control of myokine regulation of β-cell function, SkM biopsies were taken from non-diabetic (ND) and Type 2 diabetic (T2D) subjects and satellite cells cultured to myotubes (MT). MT were also treated with lipopolysaccharide (infectious inflammation-II) or a combination of glucose (10 mM), insulin (120 pM), and palmitate (0.4 mM) (metabolic inflammation-MI) to model the inflammatory and metabolic conditions seen in vivo with T2D. Conditioned media (CM) was collected from MT after 24 h and used to treat INS-1 cells for 24 h. Cell viability, total insulin content, glucose-stimulated insulin secretion (GSIS) and maximal (IBMX-stimulated) IS (IS max) were monitored. Under baseline conditions, CM from ND and T2D MT had no effects on INS-1 cell viability, insulin content, GSIS, or IS max. After exposure to II, CM from ND-MT augmented GSIS in INS-1 cells by 100 ± 25% over control (p < 0.05); T2D-CM had no effect. After exposure to MI, T2D-CM suppressed GSIS by 35 ± 5% (p < 0.05); ND-CM was without effect. Under either of these conditions cell viability, total insulin content and IS max were unaffected. Effects of CM on GSIS were lost after CM was boiled. Both augmentation of GSIS by ND-CM from II-treated MT, and suppression by T2D-CM from MI-treated MT, were inhibited by wortmannin, Ro 31-8220, and SB203580. In summary: (1) ND-MT are able to augment GSIS when stressed, (2) T2D-MT responding to a diabetic-like environment secrete myokines that suppress GSIS, (3) Unknown protein factors exert effects specifically on GSIS, possibly through PI-3K, PKC, and/or p38 MAPK. In T2D, both insulin resistance and a suppression of adaptive increased insulin secretion are intrinsic properties of SkM that can contribute to the full T2D phenotype.

The importance of exercise for glycemic control in type 2 diabetes

“…Further, mitochondrial function within the beta-cell cell may be involved, 28 and muscles may relase cytokines that influence beta-cell mass and/or function. 56 In either case, these studies align with current ACSM and ADA guidelines recommending concurrent training and the inclusion of at least 2 resistance training days in a week, as part of reaching at least 150 min of moderate intensity exercise to impact glycemia.…”

Changes in Skeletal Muscle PAK1 Levels Regulate Tissue Crosstalk to Impact Whole Body Glucose Homeostasis

“…More recently, attention has been raised to a role for skeletal muscle in regulating b-cell mass and function. Conditioned media studies using human T2D skeletal muscle cells have demonstrated that myokines from the skeletal muscle can modulate GSIS in INS-1 832/13 b-cells (46); the presence of myokines could be an explanation for why GSIS was boosted in INS-1 832/13 b-cells treated with CM collected from myotubes overexpressing PAK1. In addition, exercise training has been shown to increase GSIS (47).…”

The relationship between different C-peptide level and insulin dose of insulin pump

“…However, few studies have been conducted on the initial dosage setting of pump insulin in T2DM, and most of these have mainly referred to the normal human insulin secretion mode and the application of patients with T1DM in foreign countries 8 . Previous studies 10 – 12 have suggested that patients with good reserved β-cell function in the remaining islets would benefit more after intensive therapy. However, there is no simple index for the quantitative evaluation of the function of reserved islets.…”