scholarly journals Polymorphisms of the Insulin Receptor Subtrate-2 in Patients with Type 2 Diabetes

2003 ◽  
Vol 88 (1) ◽  
pp. 317-322 ◽  
Author(s):  
Rossella D’Alfonso ◽  
Maria Adelaide Marini ◽  
Lucia Frittitta ◽  
Roberto Sorge ◽  
Simona Frontoni ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Insulin Receptor ◽  
Central Italy ◽  
Allelic Frequency ◽  
Diabetic Patients ◽  
Lazio Region ◽  
South Italy ◽  
Glucose Tolerant

We investigated the significance of Gly1057Asp and Leu647Val insulin receptor substrate (IRS)-2 polymorphisms in two Italian cohorts comprising 186 glucose-tolerant subjects and 240 subjects with type 2 diabetes from the Lazio region (i.e. representative of central Italy), and 123 glucose-tolerant subjects from the Sicily region (i.e. representative of south Italy). The allelic frequency of Gly1057Asp variant did not differ between diabetics (32.9%) and nondiabetic subjects, whatever their ethnicity was (35.8% and 33.7% from Lazio and Sicily, respectively). As compared with Gly/Gly subjects within each group, Asp/Asp individuals showed no differences in quantitative traits, including fasting insulin and C-peptide, and several indices of insulin sensitivity and secretion. Only one of the diabetic patients was heterozygous for the Leu647Val variant, and none of the control subjects carried this variant. This patient had three children who were also heterozygous for this variant. They were glucose tolerant, and their insulin sensitivity and insulin secretion indices were within the range of age-matched controls. We also analyzed IRS-2 function in fibroblasts from carriers of Gly1057Asp or Leu647Val variant. No defects in IRS-2 expression, insulin-stimulated phosphorylation, or binding to the p85 subunit of phosphatidylinositol 3-kinase were observed. These results strongly argue against a major role of IRS-2 polymorphisms in the pathogenesis of type 2 diabetes.

scholarly journals Common Risk Factors in Relatives and Spouses of Patients with Type 2 Diabetes in Developing Prediabetes

Healthcare ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1010
Author(s):  
Wei-Hao Hsu ◽  
Chin-Wei Tseng ◽  
Yu-Ting Huang ◽  
Ching-Chao Liang ◽  
Mei-Yueh Lee ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Cell Function ◽  
Diabetic Patients ◽  
Β Cell ◽  
Tyg Index ◽  
Β Cell Function

Prediabetes should be viewed as an increased risk for diabetes and cardiovascular disease. In this study, we investigated its prevalence among the relatives and spouses of patients with type 2 diabetes or risk factors for prediabetes, insulin resistance, and β-cell function. A total of 175 individuals were included and stratified into three groups: controls, and relatives and spouses of type 2 diabetic patients. We compared clinical characteristics consisting of a homeostatic model assessment for insulin resistance (HOMA-IR) and beta cell function (HOMA-β), a quantitative insulin sensitivity check index (QUICKI), and triglyceride glucose (TyG) index. After a multivariable linear regression analysis, the relative group was independently correlated with high fasting glucose, a high TyG index, and low β-cell function; the relatives and spouses were independently associated with a low QUICKI. The relatives and spouses equally had a higher prevalence of prediabetes. These study also indicated that the relatives had multiple factors predicting the development of diabetes mellitus, and that the spouses may share a number of common environmental factors associated with low insulin sensitivity.

Effect of 10 days of bedrest on metabolic and vascular insulin action: a study in individuals at risk for type 2 diabetes

2010 ◽  
Vol 108 (4) ◽  
pp. 830-837 ◽  
Author(s):  
Mette P. Sonne ◽  
Amra C. Alibegovic ◽  
Lise Højbjerre ◽  
Allan Vaag ◽  
Bente Stallknecht ◽  
...  
Keyword(s):  
Physical Activity ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
High Sensitivity ◽  
Whole Body ◽  
Diabetic Patients ◽  
Activity Levels ◽  
Type 2 Diabetic Patients ◽  
Increased Risk

Physical inactivity is a known risk factor for type 2 diabetes. We studied whole body and forearm insulin sensitivity in subjects at increased risk for type 2 diabetes [persons with low birth weight (LBW group; n = 20) and first-degree relatives to type 2 diabetic patients (FDR group; n = 13)] as well as a control (CON) group ( n = 20) matched for body mass index, age, and physical activity levels before and after 10 days of bedrest. Subjects were studied by hyperinsulinemic isoglycemic clamp combined with arterial and deep venous catheterization of the forearm. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. All groups responded with a decrease in whole body insulin sensitivity in response to bedrest [CON group: 6.8 ± 0.5 to 4.3 ± 0.3 mg·min−1·kg−1( P < 0.0001), LBW group: 6.2 ± 0.5 to 4.3 ± 0.3 mg·min−1·kg−1( P < 0.0001), and FDR group: 4.3 ± 0.7 to 3.1 ± 0.3 mg·min−1·kg−1( P = 0.068)]. The percent decrease was significantly greater in the CON group compared with the FDR group (CON group: 34 ± 4%, LBW group: 27 ± 4%, and FDR group: 10 ± 13%). Forearm insulin-stimulated glucose clearance decreased significantly in the CON and LBW groups in response to bedrest; in the FDR group, clearance was very low before bedrest and no change was observed. Before bedrest, the CON and LBW groups demonstrated a significant increase in FBF during hyperinsulinemia; after bedrest, an increase in FBF was observed only in the CON group. In conclusion, bedrest induced a pronounced reduction in whole body, skeletal muscle, and vascular insulin sensitivity in the CON and LBW groups. The changes were most pronounced in the CON group. In the FDR group, insulin resistance was already present before bedrest, but even this group displayed a high sensitivity to changes in daily physical activity.

Relationship between Serum Butyrylcholinesterase Activity, Hypertriglyceridaemia and Insulin Sensitivity in Diabetes Mellitus

1993 ◽  
Vol 85 (1) ◽  
pp. 77-81 ◽  
Author(s):  
C. A. Abbott ◽  
M. I. MacKness ◽  
S. Kumar ◽  
A. O. Olukoga ◽  
C. Gordon ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Lipoprotein Metabolism ◽  
Diabetic Patients ◽  
Control Subjects ◽  
Triacylglycerol Concentration ◽  
Butyrylcholinesterase Activity

1. The activity of serum butyrylcholinesterase (‘pseudocholinesterase’, EC3.1.1.8) was investigated in 56 patients with type 1 diabetes mellitus, 51 patients with type 2 diabetes mellitus and 101 healthy control subjects. 2. Butyrylcholinesterase activity was significantly elevated in both type 1 (8.10 ± 3.35 units/ml) and type 2 (7.22 ± 1.95 units/ml) diabetes compared with the control subjects (4.23 ± 1.89 units/ml) (P <0.001). 3. In the patients with type 1 and type 2 diabetes, serum butyrylcholinesterase activity was correlated with log serum fasting triacylglycerol concentration (r = 0.41 and r = 0.43, respectively, P <0.001). In the type 2 population serum butyrylcholinesterase activity was also correlated with insulin sensitivity (r = −0.51, P <0.001). 4. Serum butyrylcholinesterase activity was unrelated to age, gender, serum γ-glutamyltranspeptidase activity, body mass index, or treatment for diabetes in both the diabetic populations. 5. In 37 non-diabetic patients with butyrylcholinesterase deficiency serum triacylglycerol levels were in the normal range. 6. These results are consistent with the view that butyrylcholinesterase may have a role in the altered lipoprotein metabolism in hypertriglyceridaemia associated with insulin insensitivity or insulin deficiency in diabetes mellitus.

Effects of Physical Training on Metabolic Control in Elderly Type 2 Diabetes Mellitus Patients

1997 ◽  
Vol 93 (2) ◽  
pp. 127-135 ◽  
Author(s):  
P.C. Ligtenberg ◽  
J.B.L. Hoekstra ◽  
E. Bol ◽  
M.L. Zonderland ◽  
D.W. Erkelens
Keyword(s):  
Physical Activity ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Physical Training ◽  
Training Group ◽  
Control Group ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic

1. The specific role of physical activity in the treatment of type 2 diabetes is still subject to discussion. A randomized prospective study was performed, investigating both the influence of physical training on metabolic control and the feasibility of physical training in the elderly. 2. A total of 58 patients (mean age: 62 ± 5 years; range: 55–75 years) with type 2 diabetes were randomized to either a physical training or a control programme. The training programme consisted of three sessions a week, aiming at 60–80% of the maximal oxygen uptake (VO2max). The 12 week supervised period was followed by a 14 week non-supervised one. The control group followed an educational programme. VO2max was assessed during exercise on a cycle ergometer. Glycosylated haemoglobin (HbA1c) was used as a measure for glucose control, and an insulin tolerance test was performed to test insulin sensitivity. Multivariate analysis of variance, with repeated measures design, was used to test differences between groups. 3. Fifty-one patients completed the study. VO2max was higher in the training group than in the control group both after 6 weeks (P ≤ 0.01 between groups) and after 26 weeks [training group: 1796 ± 419 ml/min (prestudy), 1880 ± 458 ml/min (6 weeks), 1786 ± 591 ml/min (26 weeks); control group: 1859 ± 455 ml/min (prestudy), 1742 ± 467 ml/min (6 weeks), 1629 ± 504 ml/min (26 weeks)]. Blood glucose control and insulin sensitivity did not change during the study. Levels of total triacyl-glycerols, very-low-density lipoprotein-triacyl-glycerols and apolipoprotein B were significantly lower after 6 weeks (P ≤ 0.01, P ≤ 0.05, P ≤ 0.05 between groups respectively), and so was the level of total cholesterol after 12 weeks of training (P ≤ 0.05 between groups). 4. Physical training in obese type 2 diabetic patients over 55 years of age does not change glycaemic control or insulin sensitivity in the short-term. Regular physical activity may lower triacylglycerol and cholesterol levels in this group of patients. 5. Finally, physical training in motivated elderly type 2 diabetic patients without major cardiovascular or musculoskeletal disorders is feasible, but only under supervision.

scholarly journals Impaired Muscle Regeneration in Ob/ob and Db/db Mice

2011 ◽  
Vol 11 ◽  
pp. 1525-1535 ◽  
Author(s):  
Mai-Huong Nguyen ◽  
Ming Cheng ◽  
Timothy J. Koh
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Muscle Regeneration ◽  
High Fat Diet ◽  
Diabetic Patients ◽  
High Fat ◽  
Type 2 Diabetic Patients ◽  
Macrophage Accumulation

In obesity and type 2 diabetes, efficient skeletal muscle repair following injury may be required, not only for restoring muscle structure and function, but also for maintaining exercise capacity and insulin sensitivity. The hypothesis of this study was that muscle regeneration would be impaired in ob/ob and db/db mice, which are common mouse models of obesity and type 2 diabetes. Muscle injury was produced by cardiotoxin injection, and regeneration was assessed by morphological and immunostaining techniques. Muscle regeneration was delayed in ob/ob and db/db mice, but not in a less severe model of insulin resistance – feeding a high-fat diet to wild-type mice. Angiogenesis, cell proliferation, and myoblast accumulation were also impaired in ob/ob and db/db mice, but not the high-fat diet mice. The impairments in muscle regeneration were associated with impaired macrophage accumulation; macrophages have been shown previously to be required for efficient muscle regeneration. Impaired regeneration in ob/ob and db/db mice could be due partly to the lack of leptin signaling, since leptin is expressed both in damaged muscle and in cultured muscle cells. In summary, impaired muscle regeneration in ob/ob and db/db mice was associated with reduced macrophage accumulation, angiogenesis, and myoblast activity, and could have implications for insulin sensitivity in the skeletal muscle of obese and type 2 diabetic patients.

scholarly journals Heterozygous knockout of the IRS-1 gene in mice enhances obesity-linked insulin resistance: a possible model for the development of type 2 diabetes

2002 ◽  
Vol 174 (2) ◽  
pp. 309-319 ◽  
Author(s):  
A Shirakami ◽  
T Toyonaga ◽  
K Tsuruzoe ◽  
T Shirotani ◽  
K Matsumoto ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Receptor ◽  
Tolerance Test ◽  
Diabetic Patients ◽  
Fasting Insulin ◽  
Type 2 Diabetic Patients ◽  
Gold Thioglucose ◽  
The Impact

Insulin receptor substrate 1 (IRS-1) gene polymorphisms have been identified in type 2 diabetic patients; however, it is unclear how such polymorphisms contribute to the development of diabetes. Here we introduced obesity in heterozygous IRS-1 knockout (IRS-1(+/-)) mice by gold-thioglucose (GTG) injection and studied the impact of reduced IRS-1 expression on obesity-linked insulin resistance. GTG injection resulted in approximately 30% weight gain in IRS-1(+/-) and wild type (WT) mice, compared with saline-injected controls. There was no difference in insulin sensitivity between lean IRS-1(+/-) and lean WT. Elevated fasting insulin levels but no change in fasting glucose were noted in obese IRS-1(+/-) and WT compared with the respective lean controls. Importantly, fasting insulin in obese IRS-1(+/-) was 1.5-fold higher (P<0.05) than in obese WT, and an insulin tolerance test showed a profound insulin resistance in obese IRS-1(+/-) compared with obese WT. The islets of obese IRS-1(+/-) were 1.4-fold larger than those of obese WT. The expression of insulin receptor and IRS-1 and IRS-2 was decreased in obese IRS-1(+/-), which could in part explain the profound insulin resistance in these mice. Our results suggest that IRS-1 is the suspected gene for type 2 diabetes and its polymorphisms could worsen insulin resistance in the presence of other additional factors, such as obesity.

scholarly journals Relationship between Serum Lipoprotein Ratios and Insulin Resistance in Obesity

2004 ◽  
Vol 50 (12) ◽  
pp. 2316-2322 ◽  
Author(s):  
Attila Brehm ◽  
Georg Pfeiler ◽  
Giovanni Pacini ◽  
Heinrich Vierhapper ◽  
Michael Roden
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Serum Lipid ◽  
Fasting Serum ◽  
Lipid Ratios ◽  
Glucose Tolerant

Abstract Background: The fasting serum lipid profile [triglycerides (TGs), total cholesterol (TC), and LDL- and HDL-cholesterol (LDL-C and HDL-C)] is used to calculate lipid ratios (TC/HDL-C, LDL-C/HDL-C, TG/HDL-C) that allow identification of individuals at increased risk for cardiovascular disease. Because these individuals are also frequently insulin resistant, this study analyzed the relationships between lipid ratios and insulin sensitivity. Methods: In 132 obese [mean (SE) body mass index, 37.5 (0.6) kg/m2] outpatients without known diabetes mellitus, fasting serum lipid profiles and 75-g oral glucose tolerance tests were performed. Insulin sensitivity was assessed from surrogate estimates for fasting (QUICKI) and dynamic (OGIS) conditions. Results: After exclusion of other endocrine diseases (n = 35), the remaining patients were classified as glucose tolerant (n = 56), glucose intolerant (n = 22), or as having type 2 diabetes (n = 19). QUICKI and OGIS indicated severe insulin resistance in all individuals with type 2 diabetes and impaired glucose tolerance compared with glucose-tolerant individuals: QUICKI, glucose tolerant, 0.302 (0.002); glucose intolerant, 0.290 (0.002); type 2 diabetes, 0.281 (0.005); P &lt;0.001; OGIS (mL · m−2 · min−1), glucose tolerant, 343 (7), glucose intolerant, 293 (9); type 2 diabetes, 256 (12); P &lt;0.001. Serum TG (P &lt;0.005) and TG/HDL-C ratios (P &lt;0.05) were increased in individuals with impaired glucose tolerance. TG/HDL-C ratios negatively correlated with QUICKI (r = −0.370; P &lt; 0.001) and OGIS (r = −0.333; P &lt; 0.005) in nondiabetic individuals (glucose tolerant plus glucose intolerant), but not in patients with type 2 diabetes (not significant). Conclusions: This study demonstrates that the TG/HDL-C ratio positively correlates with insulin resistance in severely obese nondiabetic individuals.

Increased subsarcolemmal lipids in type 2 diabetes: effect of training on localization of lipids, mitochondria, and glycogen in sedentary human skeletal muscle

2010 ◽  
Vol 298 (3) ◽  
pp. E706-E713 ◽  
Author(s):  
Joachim Nielsen ◽  
Martin Mogensen ◽  
Birgitte F. Vind ◽  
Kent Sahlin ◽  
Kurt Højlund ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Aerobic Training ◽  
Diabetic Patients ◽  
Vastus Lateralis Muscle ◽  
Inverse Association ◽  
Type 2 Diabetic Patients ◽  
Pronounced Increase ◽  
Type 2 Diabetic

The purpose of the study was to investigate the effect of aerobic training and type 2 diabetes on intramyocellular localization of lipids, mitochondria, and glycogen. Obese type 2 diabetic patients ( n = 12) and matched obese controls ( n = 12) participated in aerobic cycling training for 10 wk. Endurance-trained athletes ( n = 15) were included for comparison. Insulin action was determined by euglycemic-hyperinsulinemic clamp. Intramyocellular contents of lipids, mitochondria, and glycogen at different subcellular compartments were assessed by transmission electron microscopy in biopsies obtained from vastus lateralis muscle. Type 2 diabetic patients were more insulin resistant than obese controls and had threefold higher volume of subsarcolemmal (SS) lipids compared with obese controls and endurance-trained subjects. No difference was found in intermyofibrillar lipids. Importantly, following aerobic training, this excess SS lipid volume was lowered by ∼50%, approaching the levels observed in the nondiabetic subjects. A strong inverse association between insulin sensitivity and SS lipid volume was found ( r2=0.62, P = 0.002). The volume density and localization of mitochondria and glycogen were the same in type 2 diabetic patients and control subjects, and showed in parallel with improved insulin sensitivity a similar increase in response to training, however, with a more pronounced increase in SS mitochondria and SS glycogen than in other localizations. In conclusion, this study, estimating intramyocellular localization of lipids, mitochondria, and glycogen, indicates that type 2 diabetic patients may be exposed to increased levels of SS lipids. Thus consideration of cell compartmentation may advance the understanding of the role of lipids in muscle function and type 2 diabetes.

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