Increments in insulin sensitivity during intensive treatment are closely correlated with decrements in glucocorticoid receptor mRNA in skeletal muscle from patients with Type II diabetes

2001 ◽  
Vol 101 (5) ◽  
pp. 533-540 ◽  
Author(s):  
Henrik VESTERGAARD ◽  
Palle BRATHOLM ◽  
Niels Juel CHRISTENSEN
Keyword(s):  
Skeletal Muscle ◽  
Type Ii Diabetes ◽  
Intensive Treatment ◽  
Whole Body ◽  
Glucose Disposal ◽  
Diabetic Patients ◽  
Mrna Levels ◽  
Type Ii ◽  
Total Rna ◽  
Glucose Disposal Rate

To test the hypothesis that changes in the expression of the glucocorticoid receptor (GCR) and the β2-adrenoceptor (β2-AR) contribute significantly to the abnormal glucose metabolism in skeletal muscle from patients with Type II diabetes, we have examined (1) the levels of total GCR (α+β isoforms), the α/α2 isoform of GCR and β2-AR mRNAs in skeletal muscle from insulin-resistant patients with Type II diabetes (n = 10) and healthy controls (n = 15), and (2) the effects of 8 weeks of intensive treatment on the whole-body glucose disposal rate and on total GCR, α/α2 GCR and β2-AR mRNA levels in diabetic patients. The total glucose disposal rate was measured by the euglycaemic hyperinsulinaemic (2m-unitsċmin-1ċkg-1) clamp technique, and mRNA levels were assessed by reverse transcriptase-PCR and HPLC for separation of standard and unknown and quantification. Mean levels of total GCR and α/α2 GCR mRNAs were increased in patients with Type II diabetes when compared with control subjects [total GCR, 2.06±0.30 and 1.47±0.10 amol/μg of total RNA respectively (P = 0.09); α/α2 GCR mRNA, 1.69±0.31and 0.92±0.09amol/μg of total RNA respectively (P = 0.02)], whereas mRNA levels of the β isoform of GCR (total GCR minus α/α2 GCR) were decreased (P = 0.006). β2-AR mRNA levels were comparable in diabetic patients and control subjects (0.53±0.05 and 0.45±0.02amol/μg of total RNA respectively; P = 0.2). Intensive treatment for 8 weeks was associated with improved glycaemic control (P = 0.019), and during the clamp a 75% (P = 0.001) increase in the whole-body insulin-stimulated glucose disposal rate was demonstrated. Total GCR (P = 0.005), α/α2 GCR (P = 0.005) and β2-AR (P = 0.03) mRNA levels all decreased significantly after intensive insulin treatment. A close correlation was found between increments in glucose uptake during intensive treatment and decrements in skeletal muscle total GCR mRNA (r = 0.95, P<0.001; multiple regression analysis), and between glucose uptake and α/α2 GCRm RNA levels (r = 0.88, P<0.001; simple correlation). In conclusion, the abnormal regulation of GCR mRNA is likely to play a significant role in the insulin resistance observed in obese patients with Type II diabetes.

Insulin signal transduction in human skeletal muscle: identifying the defects in Type II diabetes

2005 ◽  
Vol 33 (2) ◽  
pp. 354-357 ◽  
Author(s):  
M. Björnholm ◽  
J.R. Zierath
Keyword(s):  
Skeletal Muscle ◽  
Type Ii Diabetes ◽  
Insulin Action ◽  
Glucose Transporter ◽  
Whole Body ◽  
Diabetic Patients ◽  
Type Ii ◽  
Peripheral Tissues ◽  
Glucose Homoeostasis ◽  
Insulin Receptor Signalling

Type II diabetes is characterized by defects in insulin action on peripheral tissues, such as skeletal muscle, adipose tissue and liver and pancreatic β-cell defects. Since the skeletal muscle accounts for approx. 75% of whole body insulin-stimulated glucose uptake, defects in this tissue play a major role in the impaired glucose homoeostasis in Type II diabetic patients. Thus identifying defective steps in this process may reveal attractive targets for drug development to combat insulin resistance and Type II diabetes. This review will describe the effects of insulin on glucose transport and other metabolic events in skeletal muscle that are mediated by intracellular signalling cascades. Evidence for impaired activation of the insulin receptor signalling cascade and defective glucose transporter 4 translocation in the skeletal muscle from Type II diabetic patients will be presented. Through the identification of the intracellular defects in insulin action that control glucose homoeostasis, a better understanding of the disease pathogenesis can be gained and strategies for intervention may be developed.

Effects of Type II diabetes on capillary hemodynamics in skeletal muscle

2006 ◽  
Vol 291 (5) ◽  
pp. H2439-H2444 ◽  
Author(s):  
Danielle J. Padilla ◽  
Paul McDonough ◽  
Brad J. Behnke ◽  
Yutaka Kano ◽  
K. Sue Hageman ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Glucose ◽  
Type Ii Diabetes ◽  
Capillary Tube ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Diabetic Patients ◽  
Type I ◽  
Type Ii ◽  
Gk Rats

Microcirculatory red blood cell (RBC) hemodynamics are impaired within skeletal muscle of Type I diabetic rats (Kindig CA, Sexton WL, Fedde MR, and Poole DC. Respir Physiol 111: 163–175, 1998). Whether muscle microcirculatory dysfunction occurs in Type II diabetes, the more prevalent form of the disease, is unknown. We hypothesized that Type II diabetes would reduce the proportion of capillaries supporting continuous RBC flow and RBC hemodynamics within the spinotrapezius muscle of the Goto-Kakizaki Type II diabetic rat (GK). With the use of intravital microscopy, muscle capillary diameter ( dc), capillary lineal density, capillary tube hematocrit (Hctcap), RBC flux ( FRBC), and velocity ( VRBC) were measured in healthy male Wistar (control: n = 5, blood glucose, 105 ± 5 mg/dl) and male GK ( n = 7, blood glucose, 263 ± 34 mg/dl) rats under resting conditions. Mean arterial pressure did not differ between groups ( P > 0.05). Sarcomere length was set to a physiological length (∼2.7 μm) to ensure that muscle stretching did not alter capillary hemodynamics; dc was not different between control and GK rats ( P > 0.05), but the percentage of RBC-perfused capillaries (control: 93 ± 3; GK: 66 ± 5 %), Hctcap, VRBC, FRBC, and O2 delivery per unit of muscle were all decreased in GK rats ( P < 0.05). This study indicates that Type II diabetes reduces both convective O2 delivery and diffusive O2 transport properties within muscle microcirculation. If these microcirculatory deficits are present during exercise, it may provide a basis for the reduced O2 exchange characteristic of Type II diabetic patients.

Relationship between uric acid and creatinine in pre-diabetic and diabetic patients: Vidarbha region of Maharashtra

2020 ◽  
Vol 11 (3) ◽  
pp. 3412-3417
Author(s):  
Ranjit S. Ambad ◽  
Rakesh Kumar Jha ◽  
Lata Kanyal Butola ◽  
Nandkishor Bankar ◽  
Brij Raj Singh ◽  
...  
Keyword(s):  
Uric Acid ◽  
Serum Uric Acid ◽  
Type Ii Diabetes ◽  
Fasting Blood Glucose ◽  
General Medicine ◽  
Control Group ◽  
Diabetic Patients ◽  
Type Ii ◽  
Develop Type ◽  
Low Levels

Prediabetes is a glucose homeostasis condition characterized by decreased absorption to glucose or reduced fasting glucose. Both of these are reversible stages of intermediate hyperglycaemia providing an increased type II DM risk. Pre-diabetes can therefore be viewed as a significant reversible stage which could lead to type II DM, and early detection of prediabetes may contribute to type II DM prevention. Prediabetes patients are at high risk for potential type II diabetes, and 70 percent of them appear to develop Type II diabetes within 10 years. The present study includes total 200 subjects that include 100 Prediabetic patients, 50 T2DM patients and 50 healthy individual. Blood samples were collected from the subjects were obtained for FBS, PPBS, Uric acid and Creatinine estimation, from OPD and General Medicine Wards. Present study showed low levels of Serum Uric Acid in prediabetic and T2DM patients were decreased as compared to control group, while the level of creatinine in prediabetic and diabetic were elevated as compared to control group, were not statically significant. Serum Uric Acid was high in control group and low in prediabetic and diabetic patients. Serum creatinine was declined in control group and increased in prediabetic and diabetic patients with increasing Fasting blood glucose level.

Neural control of glucose uptake by skeletal muscle after central administration of NMDA

1995 ◽  
Vol 268 (2) ◽  
pp. R492-R497 ◽  
Author(s):  
C. H. Lang ◽  
M. Ajmal ◽  
A. G. Baillie
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Glucose Uptake ◽  
Neural Control ◽  
Plasma Insulin ◽  
Regional Blood Flow ◽  
Muscle Blood Flow ◽  
Whole Body ◽  
Glucose Disposal ◽  
Central Administration

Intracerebroventricular injection of N-methyl-D-aspartate (NMDA) produces hyperglycemia and increases whole body glucose uptake. The purpose of the present study was to determine in rats which tissues are responsible for the elevated rate of glucose disposal. NMDA was injected intracerebroventricularly, and the glucose metabolic rate (Rg) was determined for individual tissues 20-60 min later using 2-deoxy-D-[U-14C]glucose. NMDA decreased Rg in skin, ileum, lung, and liver (30-35%) compared with time-matched control animals. In contrast, Rg in skeletal muscle and heart was increased 150-160%. This increased Rg was not due to an elevation in plasma insulin concentrations. In subsequent studies, the sciatic nerve in one leg was cut 4 h before injection of NMDA. NMDA increased Rg in the gastrocnemius (149%) and soleus (220%) in the innervated leg. However, Rg was not increased after NMDA in contralateral muscles from the denervated limb. Data from a third series of experiments indicated that the NMDA-induced increase in Rg by innervated muscle and its abolition in the denervated muscle were not due to changes in muscle blood flow. The results of the present study indicate that 1) central administration of NMDA increases whole body glucose uptake by preferentially stimulating glucose uptake by skeletal muscle, and 2) the enhanced glucose uptake by muscle is neurally mediated and independent of changes in either the plasma insulin concentration or regional blood flow.

Influence of short-term dexfenfluramine therapy on glucose and lipid metabolism in obese non-diabetic patients

1993 ◽  
Vol 128 (3) ◽  
pp. 251-258 ◽  
Author(s):  
Per H Andersen ◽  
Bjørn Richelsen ◽  
Jens Bak ◽  
Ole Schmitz ◽  
Niels S Sørensen ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Serum Insulin ◽  
Whole Body ◽  
Glucose Disposal ◽  
Total Serum ◽  
Total Serum Cholesterol ◽  
Diabetic Patients ◽  
Obese Patients ◽  
Short Term ◽  
Glucose And Lipid Metabolism

In a short-term (eight days) double-blind crossover study involving 10 obese patients, the effects of dexfenfluramine on glucose and lipid metabolism were examined. The protocol comprised whole body in vivo measurements (hyperinsulinemic euglycemic clamp in combination with indirect calorimetry) and in vitro studies of isolated adipocytes (lipolysis and glucose transport). All study participants were weight stable during the study period (103.1±3.2, placebo vs 103.3±3.1 kg, dexfenfluramine, NS). The following parameters were significantly reduced after dexfenfluramine treatment: fasting levels of plasma glucose (6.2±0.2 vs 5.7±0.2 mmol/l, p<0.01), serum insulin (168.0±14.5 vs 138.9±7.9 pmol/l, p<0.05), serum C-peptide (0.68±0.03 vs 0.58±0.02 nmol/l, p<0.05) and total serum cholesterol (6.07±0.41 vs 5.48±0.38 mmol/l, p< 0.01). In the basal state glucose oxidation rate was significantly reduced by 36% (p<0.001), whereas non-oxidative glucose disposal was significantly increased by 41% (p<0.01), following dexfenfluramine treatment. Insulin-stimulated (2 mU·kg−1·min−1) glucose disposal rate tended to be increased (18%, p=0.10) after dexfenfluramine. In conclusion, dexfenfluramine possesses beneficial regulatory effects on glucose and lipid metabolism in non-diabetic obese patients, independently of weight loss.

Localization of Rate-Limiting Defect for Glucose Disposal in Skeletal Muscle of Insulin-Resistant Type I Diabetic Patients

Diabetes ◽  
1990 ◽  
Vol 39 (2) ◽  
pp. 157-167 ◽  
Author(s):  
H. Yki-Jarvinen ◽  
K. Sahlin ◽  
J. M. Ren ◽  
V. A. Koivisto
Keyword(s):  
Skeletal Muscle ◽  
Glucose Disposal ◽  
Diabetic Patients ◽  
Type I ◽  
Insulin Resistant ◽  
Rate Limiting
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