No difference in insulin stimulated AKT and AS160 phosphorylation but decreased insulin effect on FoxO4 abundance in skeletal muscle of obese and obese type 2-diabetic subjects

Giebelstein, J; Plettig, L; Schechinger, W.; Højlund, Kurt; Levin, Klaus; Beck‐Nielsen, Henning; Klein, HH

doi:10.1055/s-0034-1371980

Cited by 1 publication

(2 citation statements)

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“…38 The role of AS160 in the regulation of GLUT translocation during diabetes and insulin resistance in striated muscle is somewhat controversial. 38,63,64 Some groups have previously reported no difference of AKT and AS160 phosphorylation during diabetes in skeletal muscle. 64 Similarly, we reported no significant change in AS160 in skeletal muscle of untreated diabetic rats.…”

Section: Discussionmentioning

confidence: 99%

“…38,63,64 Some groups have previously reported no difference of AKT and AS160 phosphorylation during diabetes in skeletal muscle. 64 Similarly, we reported no significant change in AS160 in skeletal muscle of untreated diabetic rats. In contrast, diltiazem treatment significantly decreased AS160 phosphorylation in the skeletal muscle of the treated diabetic rats.…”

Section: Discussionmentioning

confidence: 99%

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Adverse Metabolic Effects of Diltiazem Treatment During Diabetic Cardiomyopathy

Parriman

Campolo

Waller

et al. 2018

J Cardiovasc Pharmacol Ther

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Diabetes is a global epidemic disease, which leads to multiorgan dysfunction, including heart disease. Diabetes results from the limited absorption of glucose into insulin-sensitive tissues. The heart is one of the main organs to utilize glucose as an energy substrate. Glucose uptake into striated muscle is regulated by a family of membrane proteins called glucose transporters (GLUTs). Although calcium channel blockers, including diltiazem, are widely prescribed drugs for cardiovascular diseases, including in patients with diabetes, their pharmacological effects on glucose metabolism are somewhat controversial. We hypothesized that diltiazem treatment will exhibit detrimental effects on whole body glucose homeostasis and glucose transport in the striated muscle of patients with diabetes. Healthy and streptozotocin-treated rats were randomly assigned to receive diltiazem treatment or a placebo for 8 weeks. Blood glucose was significantly increased in the untreated diabetic groups, which worsened after diltiazem treatment. Diabetes decreased protein content of both GLUT4 (the predominate insulin-sensitive glucose transporter) and AS160 (Akt Substrate at 160 kDa, the downstream protein in the signaling cascade that regulates GLUT4 trafficking) in striated muscle of diabetic rats, with a more pronounced alteration after diltiazem treatment. We additionally reported that diabetic rodents displayed marked systolic dysfunction, which was not rescued by diltiazem treatment. In conclusion, diltiazem treatment worsened the effects of diabetes-induced hyperglycemia and diabetes-induced alterations in the regulation of glucose transport in striated muscle.

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