Decreased insulin secretion and increased insulin resistance are independently related to the 7-year risk of NIDDM in Mexican-Americans

Diabetes ◽  
1995 ◽  
Vol 44 (12) ◽  
pp. 1386-1391 ◽  
Author(s):  
S. M. Haffner ◽  
H. Miettinen ◽  
S. P. Gaskill ◽  
M. P. Stern
2011 ◽  
Vol 301 (2) ◽  
pp. E402-E408 ◽  
Author(s):  
Mark O. Goodarzi ◽  
Jinrui Cui ◽  
Yii-Der I. Chen ◽  
Willa A. Hsueh ◽  
Xiuqing Guo ◽  
...  

Several processes contribute to variation in fasting insulin concentration, including fasting glucose, insulin resistance, insulin secretion, and insulin clearance. Our goal was to determine the relative contribution of each of these insulin-related traits, plus anthropometric parameters, to fasting insulin among 470 Mexican Americans. The euglycemic hyperinsulinemic clamp yielded insulin sensitivity (M value) and metabolic clearance rate of insulin (MCRI). Acute insulin secretion was estimated by the insulinogenic index (IGI30) from the oral glucose tolerance test. Regression (univariate) and generalized estimating equations (multivariate) were used to describe the relationship of insulin-related traits to fasting insulin. Univarate analyses were used to select which traits to include in the multivariate model. In multivariate analysis, MCRI, M, BMI, waist circumference, and fasting glucose were independently associated with fasting insulin. Decreasing M and MCRI were associated with increasing fasting insulin, whereas increasing BMI, waist circumference, and fasting glucose were associated with increasing fasting insulin. Standardized coefficients allowed determination of the relative strength of each trait's association with fasting insulin in the entire cohort (strongest to weakest): MCRI (−0.35, P < 0.0001), M (−0.24, P < 0.0001), BMI (0.20, P = 0.0011), waist circumference (0.16, P = 0.021), and fasting glucose (0.11, P = 0.014). Fasting insulin is a complex phenotype influenced by several independent processes, each of which might have its own environmental and genetic determinants. One of the most associated traits was insulin clearance, which has implications for studies that have used fasting insulin as a surrogate for insulin resistance.


Diabetes ◽  
1995 ◽  
Vol 44 (12) ◽  
pp. 1386-1391 ◽  
Author(s):  
S. M. Haffner ◽  
H. Miettinen ◽  
S. P. Gaskill ◽  
M. P. Stern

2009 ◽  
Vol 296 (4) ◽  
pp. E758-E764 ◽  
Author(s):  
Alberto O. Chavez ◽  
Dawn K. Coletta ◽  
Subhash Kamath ◽  
Douglas T. Cromack ◽  
Adriana Monroy ◽  
...  

Retinol-binding protein-4 (RBP4), a novel protein secreted mainly by adipose tissue, has been associated with insulin resistance in obese subjects and in individuals with type 2 diabetes mellitus (T2DM). We examined the relationship between plasma RBP4 levels, expression of RBP4 in skeletal muscle and adipose tissue, and insulin sensitivity in Mexican Americans with varying degrees of obesity and glucose tolerance. Seventy-two subjects [16 lean normal-glucose-tolerant (NGT), 17 obese NGT, and 39 subjects with impaired fasting glucose/impaired glucose tolerance/T2DM] received an oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp. Insulin secretion was measured as insulinogenic index during OGTT. In a subset of subjects, hepatic glucose production was measured by 3-[3H]glucose infusion, biopsies of the vastus lateralis muscle and subcutaneous adipose tissue were obtained under basal conditions, and quantitative RT-PCR was performed to measure the RBP4 mRNA gene expression. Plasma RBP4 was significantly elevated in impaired glucose tolerance/T2DM compared with NGT lean or obese subjects. Plasma RBP4 levels correlated with 2-h glucose, triglycerides, and hemoglobin A1c. There was no association between RBP4 levels and whole body insulin sensitivity measured with either the euglycemic insulin clamp or OGTT, basal hepatic glucose production rates, and the hepatic insulin resistance index. There was no correlation between plasma RBP4 levels and indexes of insulin secretion. RBP4 mRNA expression in skeletal muscle was similar in lean NGT subjects, obese NGT subjects, and T2DM subjects. There was no difference in RBP4 mRNA expression in adipose tissue between lean and obese NGT subjects or between NGT and T2DM individuals. Plasma RBP4 levels are elevated in T2DM and associated with impaired glucose tolerance, but not associated with obesity or insulin resistance or impaired insulin secretion in Mexican Americans.


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1516-P
Author(s):  
MASAHITO YOSHINARI ◽  
YOICHIRO HIRAKAWA ◽  
JUN HATA ◽  
MAYU HIGASHIOKA ◽  
TAKANORI HONDA ◽  
...  

2020 ◽  
Vol 19 (1) ◽  
pp. 106-114
Author(s):  
Guang Hao ◽  
Xiaoyu Ma ◽  
Mengru Jiang ◽  
Zhenzhen Gao ◽  
Ying Yang

This study examined the in vivo effects of Echinops spp. polysaccharide B on type 2 diabetes mellitus in Sprague-Dawley rats. We constructed a type 2 diabetes mellitus Sprague-Dawley rat models by feeding a high-fat and high-sugar diet plus intraperitoneal injection of a small dose of streptozotocin. Using this diabetic rat model, different doses of Echinops polysaccharide B were administered orally for seven weeks. Groups receiving Xiaoke pill and metformin served as positive controls. The results showed that Echinops polysaccharide B treatment normalized the weight and blood sugar levels in the type 2 diabetes mellitus rats, increased muscle and liver glycogen content, improved glucose tolerance, increased insulin secretion, and reduced glucagon and insulin resistance indices. More importantly, Echinops polysaccharide B treatment upregulated the expression of insulin receptor in the liver, skeletal muscles, and pancreas, and significantly improved the expression levels of insulin receptor substrate-2 protein in the liver and pancreas, as well as it increased insulin receptor substrate-1 expression in skeletal muscles. These two proteins play crucial roles in increasing insulin secretion and in controlling type 2 diabetes mellitus. The findings of the present study suggest that Echinops polysaccharide B could improve the status of diabetes in type 2 diabetes mellitus rats, which may be achieved by improving insulin resistance. Our study provides a new insight into the development of a natural drug for the control of type 2 diabetes mellitus.


Author(s):  
Froylan David Martínez-Sánchez ◽  
Valerie Paola Vargas-Abonce ◽  
Andrea Rocha-Haro ◽  
Romina Flores-Cardenas ◽  
Milagros Fernández-Barrio ◽  
...  

2021 ◽  
Vol 22 (15) ◽  
pp. 7797
Author(s):  
Joseph A. M. J. L. Janssen

For many years, the dogma has been that insulin resistance precedes the development of hyperinsulinemia. However, recent data suggest a reverse order and place hyperinsulinemia mechanistically upstream of insulin resistance. Genetic background, consumption of the “modern” Western diet and over-nutrition may increase insulin secretion, decrease insulin pulses and/or reduce hepatic insulin clearance, thereby causing hyperinsulinemia. Hyperinsulinemia disturbs the balance of the insulin–GH–IGF axis and shifts the insulin : GH ratio towards insulin and away from GH. This insulin–GH shift promotes energy storage and lipid synthesis and hinders lipid breakdown, resulting in obesity due to higher fat accumulation and lower energy expenditure. Hyperinsulinemia is an important etiological factor in the development of metabolic syndrome, type 2 diabetes, cardiovascular disease, cancer and premature mortality. It has been further hypothesized that nutritionally driven insulin exposure controls the rate of mammalian aging. Interventions that normalize/reduce plasma insulin concentrations might play a key role in the prevention and treatment of age-related decline, obesity, type 2 diabetes, cardiovascular disease and cancer. Caloric restriction, increasing hepatic insulin clearance and maximizing insulin sensitivity are at present the three main strategies available for managing hyperinsulinemia. This may slow down age-related physiological decline and prevent age-related diseases. Drugs that reduce insulin (hyper) secretion, normalize pulsatile insulin secretion and/or increase hepatic insulin clearance may also have the potential to prevent or delay the progression of hyperinsulinemia-mediated diseases. Future research should focus on new strategies to minimize hyperinsulinemia at an early stage, aiming at successfully preventing and treating hyperinsulinemia-mediated diseases.


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