An in vitro human muscle preparation suitable for metabolic studies. Decreased insulin stimulation of glucose transport in muscle from morbidly obese and diabetic subjects.

Dohm, G. Lynis; Tapscott, Edward B.; Pories, Walter J.; Dabbs, David J.; Flickinger, E G; Meelheim, D; Fushiki, Tohru; Atkinson, S.; Elton, Colin; F, J

doi:10.1172/jci113622

Cited by 282 publications

(172 citation statements)

References 24 publications

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“…Very thin muscle fiber strips were incubated in vitro to make metabolic measurements, including rates of glucose transport, glycogen synthesis, and glycolysis. 6 With this preparation, we demonstrated that insulin stimulation of glucose transport, which is the limiting step in glucose utilization, is depressed in muscle7 of morbidly obese patients with or without diabetes. The degree of insulin resistance is correlated with the degree of obesity up to a body mass index of approximately 30,8 after which there is little further change.…”

Section: Discussionmentioning

confidence: 92%

“…We have documented 43 episodes of hypoglycemia in 35 patients, 6 of whom were from the NIDDM cohort, 1 from those with insulin-dependent diabetes mellitus, 8 DAY OUT FROM GASTRIC SURGERY be troublesome, with blood glucose levels as low as 27 mg/dL. We have treated these without therapeutic intervention, urging these patients to carry sugar, and most were self-limited, with corrections occurring usually within 1 year.…”

Section: Control Of Diseasementioning

confidence: 99%

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Who Would Have Thought It? An Operation Proves to Be the Most Effective Therapy for Adult-Onset Diabetes Mellitus

Pories¹,

Swanson²,

MacDonald³

et al. 1995

Annals of Surgery

2,077

1,155

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ObjectiveThis report documents that the gastric bypass operation provides long-term control for obesity and diabetes. Summary Background DataObesity and diabetes, both notoriously resistant to medical therapy, continue to be two of our most common and serious diseases. MethodsOver the last 14 years, 608 morbidly obese patients underwent gastric bypass, an operation that restricts caloric intake by (1) reducing the functional stomach to approximately 30 mL, (2) delaying gastric emptying with a c. 0.8 to 1.0 cm gastric outlet, and (3) excluding foregut with a 40 to 60 cm Roux-en-Y gastrojejunostomy. Even though many of the patients were seriously ill, the operation was performed with a perioperative mortality and complication rate of 1.5% and 8.5%, respectively. Seventeen of the 608 patients (<3%) were lost to follow-up. ResultsGastric bypass provides durable weight control. Weights fell from a preoperative mean of 304.4 lb (range, 198 The operation provides long-term control of non-insulin-dependent diabetes mellitus (NIDDM). In those patients with adequate follow-up, 121 of 146 patients (82.9%) with NIDDM and 150 of 152 patients (98.7%) with glucose impairment maintained normal levels of plasma glucose, glycosylated hemoglobin, and insulin. These antidiabetic effects appear to be due primarily to a reduction in caloric intake, suggesting that insulin resistance is a secondary protective effect rather than the initial lesion. In addition to the control of weight and NIDDM, gastric bypass also corrected or alleviated a number of other comorbidities of obesity, including hypertension, sleep apnea, cardiopulmonary failure, arthritis, and infertility. 339

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Section: Discussionmentioning

confidence: 92%

Section: Control Of Diseasementioning

confidence: 99%

Who Would Have Thought It? An Operation Proves to Be the Most Effective Therapy for Adult-Onset Diabetes Mellitus

Pories¹,

Swanson²,

MacDonald³

et al. 1995

Annals of Surgery

2,077

1,155

View full text Add to dashboard Cite

show abstract

“…Glucose homeostasis is maintained when glucose production and utilization are in balance. Skeletal muscle, the main site for glucose disposal [1] , displays decreased glucose uptake when insulin resistance occurs in T2DM patients [2,3] .…”

Section: Introductionmentioning

confidence: 99%

Astragalus polysaccharide stimulates glucose uptake in L6 myotubes through AMPK activation and AS160/TBC1D4 phosphorylation

Liu

Zhang

et al. 2012

Acta Pharmacol Sin

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Aim: To establish the mechanism responsible for the stimulation of glucose uptake by Astragalus polysaccharide (APS), extracted from Astragalus membranaceus Bunge, in L6 myotubes in vitro. Methods: APS-stimulated glucose uptake in L6 myotubes was measured using the 2-deoxy-[ 3 H]-D-glucose method. The adenine nucleotide contents in the cells were measured by HPLC. The phosphorylation of AMP-activated protein kinase (AMPK) and Akt substrate of 160 kDa (AS160) was examined using Western blot analysis. The cells transfected with 4P mutant AS160 (AS160-4P) were constructed using gene transfer approach. Results: Treatment of L6 myotubes with APS (100−1600 µg/mL) significantly increased glucose uptake in time-and concentration-dependent manners. The maximal glucose uptake was reached in the cells treated with APS (400 μg/mL) for 36 h. The APS-stimulated glucose uptake was significantly attenuated by pretreatment with Compound C, a selective AMPK inhibitor or in the cells overexpressing AS160-4P. Treatment of L6 myotubes with APS strongly promoted the activation of AMPK. We further demonstrated that either Ca 2+ /calmodulin-dependent protein kinase kinase β (CaMKKβ) or liver kinase B1 (LKB1) mediated APS-induced activation of AMPK in L6 myotubes, and the increased cellular AMP: ATP ratio was also involved. Treatment of L6 myotubes with APS robustly enhanced the phosphorylation of AS160, which was significantly attenuated by pretreatment with Compound C. Conclusion: Our results demonstrate that APS stimulates glucose uptake in L6 myotubes through the AMP-AMPK-AS160 pathway, which may contribute to its hypoglycemic effect.

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“…While insulin signalling to IRS-1 and PI 3-kinase is impaired in skeletal muscle from Type 2 diabetic patients, phosphorylation of the mitogen-activated protein kinase (MAPK) extracellular regulated kinase (ERK1/2) is normal [4,5], suggesting diversity in insulin action along metabolic and mitogenic signalling pathways in Type 2 diabetes. Impaired insulin-mediated whole body glucose uptake in Type 2 diabetes [1,2,3,4,5], as well as in several other insulin resistant states such as morbid obesity [6,7], polycystic ovary syndrome [8], gestat-MAPK's are part of a large family of related serine/threonine protein kinases that include the ERK1/2, p38 MAPK and c-jun and form a major signalling system to facilitate signal transduction to appropriate genomic, rather than direct metabolic responses [16,17]. However, p38 MAPK has recently been proposed to play a metabolic role in the regulation of insulinstimulated glucose transport by either altering the "intrinsic activity of GLUT4" or by facilitating the transition of GLUT4 from an occluded to a fully activated (exposed) state at the plasma membrane [18].…”

mentioning

confidence: 99%

Aberrant p38 mitogen-activated protein kinase signalling in skeletal muscle from Type 2 diabetic patients

2003

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Aims/hypothesis. p38 mitogen activated protein kinase (MAPK) is generally thought to facilitate signal transduction to genomic, rather than metabolic responses. However, recent evidence implicates a role for p38 MAPK in the regulation of glucose transport; a site of insulin resistance in Type 2 diabetes. Thus we determined p38 MAPK protein expression and phosphorylation in skeletal muscle from Type 2 diabetic patients and non-diabetic subjects. Methods. In vitro effects of insulin (120 nmol/l) or AI-CAR (1 mmol/l) on p38 MAPK expression and phosphorylation were determined in skeletal muscle from non-diabetic (n=6) and Type 2 diabetic (n=9) subjects. Results. p38 MAPK protein expression was similar between Type 2 diabetic patients and non-diabetic subjects.Insulin exposure increased p38 MAPK phosphorylation in non-diabetic, but not in Type 2 diabetic patients. In contrast, basal phosphorylation of p38 MAPK was increased in skeletal muscle from Type 2 diabetic patients. Conclusion/interpretation. Insulin increases p38 MAPK phosphorylation in skeletal muscle from nondiabetic subjects, but not in Type 2 diabetic patients. However, basal p38 MAPK phosphorylation is increased in skeletal muscle from Type 2 diabetic patients. Thus, aberrant p38 MAPK signalling might contribute to the pathogenesis of insulin resistance. Rapid Communication

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An in vitro human muscle preparation suitable for metabolic studies. Decreased insulin stimulation of glucose transport in muscle from morbidly obese and diabetic subjects.

Cited by 282 publications

References 24 publications

Who Would Have Thought It? An Operation Proves to Be the Most Effective Therapy for Adult-Onset Diabetes Mellitus

Who Would Have Thought It? An Operation Proves to Be the Most Effective Therapy for Adult-Onset Diabetes Mellitus

Astragalus polysaccharide stimulates glucose uptake in L6 myotubes through AMPK activation and AS160/TBC1D4 phosphorylation

Aberrant p38 mitogen-activated protein kinase signalling in skeletal muscle from Type 2 diabetic patients

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