Acquired defects of glycogen synthase activity in cultured human skeletal muscle cells: influence of high glucose and insulin levels

Henry, Robert R.; Ciaraldi, Theodore P.; Mudaliar, S.; Abrams, L.; Nikoulina, Svetlana E.

doi:10.2337/diabetes.45.4.400

Cited by 28 publications

(35 citation statements)

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“…Exposure of human myotubes to a high concentration of glucose for 8 days impaired insulin action on glycogen synthesis. Our results are consistent with previous work showing that 4 days of hyperglycaemia reduces basal [37] and insulin-stimulated glycogen synthesis [37,38].…”

Section: Discussionsupporting

confidence: 83%

Enhanced insulin-stimulated glycogen synthesis in response to insulin, metformin or rosiglitazone is associated with increased mRNA expression of GLUT4 and peroxisomal proliferator activator receptor gamma co-activator 1

Al-Khalili

Forsgren

Kannisto³

et al. 2005

Diabetologia

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Aims/hypothesis: The aim of this study was to determine the effect of several antidiabetic agents on insulin-stimulated glycogen synthesis, as well as on mRNA expression. Methods: Cultured primary human skeletal myotubes obtained from six healthy subjects were treated for 4 or 8 days without or with glucose (25 mmol/l), insulin (400 pmol/l), rosiglitazone (10 μmol/l), metformin (20 μmol/l) or the AMP-activated kinase activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) (200 μmol/l). After this, insulin-stimulated glycogen synthesis was determined. mRNA levels of the glucose transporters GLUT1 and GL UT4, the peroxisomal proliferator activator receptor gamma (PPAR gamma) co-activator 1 (PGC1) and the myocytespecific enhancer factors (MEF2), MEF2A, MEF2C and MEF2D were determined using real-time PCR analysis after 8 days exposure to the various antidiabetic agents. Results: Insulin-stimulated glycogen synthesis was significantly increased in cultured human myotubes treated with insulin, rosiglitazone or metformin for 8 days, compared with non-treated cells. Furthermore, an 8-day exposure of myotubes to 25 mmol/l glucose impaired insulin-stimulated glycogen synthesis. In contrast, treatment with AICAR was without effect on insulin-mediated glycogen synthesis. Exposure to insulin, rosiglitazone or metformin increased mRNA expression of PGC1 and GLUT4, while AICAR or 25 mmol/l glucose treatment increased GLUT1 mRNA expression. Metformin also increased mRNA expression of the MEF2 isoforms. Conclusions/ interpretation: Enhanced insulin-stimulated glycogen synthesis in human skeletal muscle cell culture coincides with increased GLUT4 and PGC1 mRNA expression following treatment with various antidiabetic agents. These data show that chronic treatment of human myotubes with insulin, metformin or rosiglitazone has a direct positive effect on insulin action and mRNA expression.

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Section: Discussionsupporting

confidence: 83%

Enhanced insulin-stimulated glycogen synthesis in response to insulin, metformin or rosiglitazone is associated with increased mRNA expression of GLUT4 and peroxisomal proliferator activator receptor gamma co-activator 1

Al-Khalili

Forsgren

Kannisto³

et al. 2005

Diabetologia

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“…tions induce insulin resistance in glycogen synthase in primary cultures of human skeletal muscle cells (10). However, it is not known whether the insulin resistance that develops secondary to hyperglycemia differentially affects specific pathways of glucose metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…The second component of the muscle insulin resistance is acquired secondary to alterations in the metabolic milieu, including elevated plasma glucose (8 -11), free fatty acid (FFA) (12)(13)(14), and insulin (15)(16)(17) levels. Experimental hyperinsulinemia has been shown to cause insulin resistance both in vitro (10,18) and in vivo (15)(16)(17)19). Similarly, a physiological elevation in plasma FFA concentrations has been shown to induce muscle insulin resistance (20 -22) Finally, chronic hyperglycemia itself is known to impair insulin action (8,9), and reversal of hyperglycemia in rats with phlorizin (23)(24)(25) improves insulin sensitivity.…”

mentioning

confidence: 99%

Normalization of Plasma Glucose Concentration by Insulin Therapy Improves Insulin-Stimulated Glycogen Synthesis in Type 2 Diabetes

et al. 2002

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Considerable evidence suggests that skeletal muscle insulin resistance is an inherent feature of type 2 diabetes and contributes to the pathogenesis of the disease. In patients with poorly controlled diabetes, hyperglycemia is thought to produce additional insulin resistance in muscle. The magnitude and nature of hyperglycemia-induced insulin resistance is not known. The purpose of the present study was to determine the biochemical mechanisms responsible for increased insulin-stimulated glucose disposal after the achievement of tight glycemic control with a mixed-split regimen. We performed hyperinsulinemic-euglycemic clamps with indirect calorimetry and vastus lateralis muscle biopsies in eight type 2 diabetic patients who had poor glycemic control (HbA 1c 10.1%) and again after 3 months of intensive insulin therapy designed to produce nearnormoglycemia (HbA 1c 6.6%). Improved glycemic control increased insulin-stimulated glucose disposal

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“…Numerous reports have described experimental paradigms for the development of insulin resistance both in vitro and in vivo. Elevation of extracellular glucose or insulin levels has been shown to inhibit insulin receptor signaling (31,42). In addition, exposure of cells to specific agents such as phorbol esters, tumor necrosis factor-␣, okadaic acid, and glucosamine also inhibit metabolic regulation by insulin (36 -38, 43, 44).…”

Section: Figmentioning

confidence: 99%

Specific Desensitization of Glycogen Synthase Activation by Insulin in 3T3-L1 Adipocytes

Jensen¹,

Crosson²,

Kartha³

et al. 2000

Journal of Biological Chemistry

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A protocol was developed in 3T3-L1 adipocytes that resulted in the specific desensitization of glycogen synthase activation by insulin. Cells were pretreated for 15 min with 100 nM insulin, and then recovered for 1.5 h in the absence of hormone. Subsequent basal and insulininduced phosphorylation of the insulin receptor, IRS-1, MAPK, Akt kinase, and GSK-3 were similar in control and pretreated cells. Additionally, enhanced glucose transport and incorporation into lipid in response to insulin were unaffected. However, pretreatment reduced insulin-stimulated glycogen synthesis by over 50%, due to a nearly complete inhibition of glycogen synthase activation. Removal of extracellular glucose during the recovery period blocked the increase in glycogen levels, and restored insulin-induced glycogen synthase activation. Furthermore, incubation of pretreated 3T3-L1 adipocytes with glycogenolytic agents reversed the desensitization event. Separation of cellular lysates on sucrose gradients revealed that glycogen synthase was primarily located in the dense pellet fraction, with lesser amounts in the lighter fractions. Insulin induced glycogen synthase translocation from the lighter to the denser glycogen-containing fractions. Interestingly, insulin preferentially activated translocated enzyme while having little effect on the majority of glycogen synthase activity in the pellet fraction. In insulin-pretreated cells, glycogen synthase did not return to the lighter fractions during recovery, and thus did not move in response to the second insulin exposure. These results suggest that, in 3T3-L1 adipocytes, the translocation of glycogen synthase may be an important step in the regulation of glycogen synthesis by insulin. Furthermore, intracellular glycogen levels can regulate glycogen synthase activation, potentially through modulation of enzymatic localization.

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Acquired defects of glycogen synthase activity in cultured human skeletal muscle cells: influence of high glucose and insulin levels

Cited by 28 publications

References 0 publications

Enhanced insulin-stimulated glycogen synthesis in response to insulin, metformin or rosiglitazone is associated with increased mRNA expression of GLUT4 and peroxisomal proliferator activator receptor gamma co-activator 1

Enhanced insulin-stimulated glycogen synthesis in response to insulin, metformin or rosiglitazone is associated with increased mRNA expression of GLUT4 and peroxisomal proliferator activator receptor gamma co-activator 1

Normalization of Plasma Glucose Concentration by Insulin Therapy Improves Insulin-Stimulated Glycogen Synthesis in Type 2 Diabetes

Specific Desensitization of Glycogen Synthase Activation by Insulin in 3T3-L1 Adipocytes

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