scholarly journals Variants in the Cav2.3 ( 1E) Subunit of Voltage-Activated Ca2+ Channels Are Associated With Insulin Resistance and Type 2 Diabetes in Pima Indians

Diabetes ◽  
2007 ◽  
Vol 56 (12) ◽  
pp. 3089-3094 ◽  
Author(s):  
Y. Li Muller ◽  
R. L. Hanson ◽  
C. Zimmerman ◽  
I. Harper ◽  
J. Sutherland ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Pima Indians ◽  
Ca2 Channels

scholarly journals PCLO Variants Are Nominally Associated With Early-Onset Type 2 Diabetes and Insulin Resistance in Pima Indians

Diabetes ◽  
2008 ◽  
Vol 57 (11) ◽  
pp. 3156-3160 ◽  
Author(s):  
L. Ma ◽  
R. L. Hanson ◽  
L. N. Que ◽  
Y. Guo ◽  
S. Kobes ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Early Onset ◽  
Pima Indians ◽  
Onset Type

scholarly journals Variants in ASK1 Are Associated With Skeletal Muscle ASK1 Expression, In Vivo Insulin Resistance, and Type 2 Diabetes in Pima Indians

Diabetes ◽  
2010 ◽  
Vol 59 (5) ◽  
pp. 1276-1282 ◽  
Author(s):  
L. Bian ◽  
R. L. Hanson ◽  
V. Ossowski ◽  
K. Wiedrich ◽  
C. C. Mason ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Pima Indians

scholarly journals Variants in ACAD10 are associated with type 2 diabetes, insulin resistance and lipid oxidation in Pima Indians

Diabetologia ◽  
2010 ◽  
Vol 53 (7) ◽  
pp. 1349-1353 ◽  
Author(s):  
L. Bian ◽  
◽  
R. L. Hanson ◽  
Y. L. Muller ◽  
L. Ma ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Lipid Oxidation ◽  
Pima Indians

scholarly journals Regulation of adipose branched-chain amino acid catabolism enzyme expression and cross-adipose amino acid flux in human obesity

2013 ◽  
Vol 304 (11) ◽  
pp. E1175-E1187 ◽  
Author(s):  
Denise E. Lackey ◽  
Christopher J. Lynch ◽  
Kristine C. Olson ◽  
Rouzbeh Mostaedi ◽  
Mohamed Ali ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Amino Acid ◽  
Metabolic Phenotype ◽  
Whole Body ◽  
Peroxisome Proliferator ◽  
Pima Indians ◽  
Obese Subjects ◽  
Branched Chain

Elevated blood branched-chain amino acids (BCAA) are often associated with insulin resistance and type 2 diabetes, which might result from a reduced cellular utilization and/or incomplete BCAA oxidation. White adipose tissue (WAT) has become appreciated as a potential player in whole body BCAA metabolism. We tested if expression of the mitochondrial BCAA oxidation checkpoint, branched-chain α-ketoacid dehydrogenase (BCKD) complex, is reduced in obese WAT and regulated by metabolic signals. WAT BCKD protein (E1α subunit) was significantly reduced by 35–50% in various obesity models ( fa/fa rats, db/db mice, diet-induced obese mice), and BCKD component transcripts significantly lower in subcutaneous (SC) adipocytes from obese vs. lean Pima Indians. Treatment of 3T3-L1 adipocytes or mice with peroxisome proliferator-activated receptor-γ agonists increased WAT BCAA catabolism enzyme mRNAs, whereas the nonmetabolizable glucose analog 2-deoxy-d-glucose had the opposite effect. The results support the hypothesis that suboptimal insulin action and/or perturbed metabolic signals in WAT, as would be seen with insulin resistance/type 2 diabetes, could impair WAT BCAA utilization. However, cross-tissue flux studies comparing lean vs. insulin-sensitive or insulin-resistant obese subjects revealed an unexpected negligible uptake of BCAA from human abdominal SC WAT. This suggests that SC WAT may not be an important contributor to blood BCAA phenotypes associated with insulin resistance in the overnight-fasted state. mRNA abundances for BCAA catabolic enzymes were markedly reduced in omental (but not SC) WAT of obese persons with metabolic syndrome compared with weight-matched healthy obese subjects, raising the possibility that visceral WAT contributes to the BCAA metabolic phenotype of metabolically compromised individuals.

scholarly journals Psammomys obesus and the albino rat-two different models of nutritional insulin resistance, representing two different types of human populations

2001 ◽  
Vol 35 (4) ◽  
pp. 346-352 ◽  
Author(s):  
R. Kalman ◽  
E. Ziv ◽  
E. Shafrir ◽  
H. Bar-On ◽  
R. Perez
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Body Weight ◽  
High Energy ◽  
Low Energy ◽  
Albino Rats ◽  
Human Populations ◽  
Psammomys Obesus ◽  
Pima Indians

Animal models for insulin resistance and type 2 diabetes are required for the study of the mechanism of these phenomena and for a better understanding of diabetes complications in human populations. Type 2 diabetes is a syndrome that affects 5-10% of the adult population. Hyperinsulinaemia, hypertriglyceridaemia, decreased high-density lipoprotein (HDL) cholesterol levels, obesity and hypertension, all form a cluster of risk factors that increase the risk of coronary artery disease, and are known as insulin resistance syndrome or syndrome X. The gerbil, Psammomys obesus is characterized by primary insulin resistance and is a well-defined model for dietary induced type 2 diabetes. Weanling Psammomys and Albino rats were held individually for several weeks on high energy (HE) and low energy (LE) diets in order to determine the development of metabolic changes leading to diabetes. Feeding Psammomys on HE diet resulted in hyperglycaemia (303 ± 40 mg/dl), hyperinsulinaemia (194 ± 31 µU/ml) and a moderate elevation in body weight, obesity and plasma triglycerides. Albino rats on HE diet demonstrated an elevation in plasma insulin (30 ± 4 µU/ml), hypertriglyceridaemia (170 µ 11 mg/dl), an elevation in body weight and obesity, but maintained normoglycaemia (98 µ 6 mg/dl). Psammomys represent a model that is similar to human populations, with primary insulin resistance expressed in young age, which leads to a high percentage of adult type 2 diabetes. Examples for such populations are the Pima Indians, Australian Aborigines and many other Third World populations. The results indicate that the metabolism of Psammomys is well adapted towards life in a low energy environment, where Psammomys takes advantage of its capacity for a constant accumulation of adipose tissue that will serve for maintenance and breeding in periods of scarcity. This metabolism known as 'thrifty metabolism', is compromised at a high nutrient intake.

The effect of insulin on net lipid oxidation predicts worsening of insulin resistance and development of type 2 diabetes mellitus

2007 ◽  
Vol 293 (1) ◽  
pp. E264-E269 ◽  
Author(s):  
Juraj Koska ◽  
Emilio Ortega ◽  
Clifton Bogardus ◽  
Jonathan Krakoff ◽  
Joy C. Bunt
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glucose Tolerance ◽  
Lipid Oxidation ◽  
Insulin Response ◽  
Pima Indians ◽  
Predictive Effect

Suppression of lipid oxidation (Lox) by insulin is impaired in obesity and type 2 diabetes mellitus (T2DM). Here we tested whether high Lox represents a primary or acquired characteristic in the pathogenesis of T2DM. Hood-indirect calorimetry was performed under postabsorptive conditions and during a two-step hyperinsulinemic euglycemic clamp (insulin infusion rates in mU·m−2·min−1: 40 low and 400 high) in 465 Pima Indians: 317 with normal glucose tolerance (NGT), 117 with impaired glucose tolerance (IGT), and 31 with T2DM. The predictive effect of net lipid oxidation (Lox) on development of T2DM was assessed in 296 subjects (51 of whom developed T2DM), whereas the predictive effect of Lox on followup changes in insulin-mediated glucose disposal (M) and acute insulin response (AIR) was studied in 190 subjects with NGT at baseline. Cross-sectionally, after adjustment for age, sex, body fat (BF), and M low, Lox low was increased in T2DM compared with NGT and IGT subjects ( P < 0.05). Prospectively, after adjustment for followup duration, age, sex, BF, M, and AIR, increased clamp Lox predicted T2DM [hazard rate ratios (95% CI): Lox low, 1.5 (1.1, 2.0), P < 0.01; Lox high, 1.3 (1.0, 1.8), P = 0.05]. High Lox low at baseline was also associated with subsequent worsening of M low ( P = 0.04). These data indicate that the inability of insulin to suppress Lox may represent an early risk marker for insulin resistance and T2DM that is independent of adiposity, acute insulin secretion, and insulin action on glucose uptake.

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