Topic
Insulin
About: Insulin is a research topic. Over the lifetime, 124295 publications have been published within this topic receiving 5129734 citations. The topic is also known as: human insulin.
Papers published on a yearly basis
Papers
More filters
TL;DR: It is shown that high doses of salicylates reverse hyperglycemia, hyperinsulinemia, and dyslipidemia in obese rodents by sensitizing insulin signaling and identifies the IKKβ pathway as a target for insulin sensitization.
Abstract: We show that high doses of salicylates reverse hyperglycemia, hyperinsulinemia, and dyslipidemia in obese rodents by sensitizing insulin signaling. Activation or overexpression of the IkappaB kinase beta (IKKbeta) attenuated insulin signaling in cultured cells, whereas IKKbeta inhibition reversed insulin resistance. Thus, IKKbeta, rather than the cyclooxygenases, appears to be the relevant molecular target. Heterozygous deletion (Ikkbeta+/-) protected against the development of insulin resistance during high-fat feeding and in obese Lep(ob/ob) mice. These findings implicate an inflammatory process in the pathogenesis of insulin resistance in obesity and type 2 diabetes mellitus and identify the IKKbeta pathway as a target for insulin sensitization.
1,897 citations
TL;DR: The observation of greatly increased postprandial plasma GLP-1 7-36 levels in patients with postgastrectomy dumping syndrome suggests that it may mediate the hyperinsulinaemia and reactive hypoglycaemia of this disorder.
1,897 citations
TL;DR: It is shown that mice with macrophage-specific deletion of the peroxisome proliferator activated receptor-γ (PPARγ) are required for maturation of alternatively activated macrophages, and gene expression profiling revealed that downregulation of oxidative phosphorylation gene expression in skeletal muscle and liver leads to decreased insulin sensitivity in these tissues.
Abstract: Obesity and insulin resistance, the cardinal features of metabolic syndrome, are closely associated with a state of low-grade inflammation. In adipose tissue chronic overnutrition leads to macrophage infiltration, resulting in local inflammation that potentiates insulin resistance. For instance, transgenic expression of Mcp1 (also known as chemokine ligand 2, Ccl2) in adipose tissue increases macrophage infiltration, inflammation and insulin resistance. Conversely, disruption of Mcp1 or its receptor Ccr2 impairs migration of macrophages into adipose tissue, thereby lowering adipose tissue inflammation and improving insulin sensitivity. These findings together suggest a correlation between macrophage content in adipose tissue and insulin resistance. However, resident macrophages in tissues display tremendous heterogeneity in their activities and functions, primarily reflecting their local metabolic and immune microenvironment. While Mcp1 directs recruitment of pro-inflammatory classically activated macrophages to sites of tissue damage, resident macrophages, such as those present in the adipose tissue of lean mice, display the alternatively activated phenotype. Despite their higher capacity to repair tissue, the precise role of alternatively activated macrophages in obesity-induced insulin resistance remains unknown. Using mice with macrophage-specific deletion of the peroxisome proliferator activated receptor-gamma (PPARgamma), we show here that PPARgamma is required for maturation of alternatively activated macrophages. Disruption of PPARgamma in myeloid cells impairs alternative macrophage activation, and predisposes these animals to development of diet-induced obesity, insulin resistance, and glucose intolerance. Furthermore, gene expression profiling revealed that downregulation of oxidative phosphorylation gene expression in skeletal muscle and liver leads to decreased insulin sensitivity in these tissues. Together, our findings suggest that resident alternatively activated macrophages have a beneficial role in regulating nutrient homeostasis and suggest that macrophage polarization towards the alternative state might be a useful strategy for treating type 2 diabetes.
1,894 citations
TL;DR: From a single glucose injection it is possible to obtain a quantitative index of insulin sensitivity that may have clinical applicability, and this index was defined as the ratio of two parameters of the chosen model and could be estimated with good reproducibility from the 300 mg/kg injection experiments.
Abstract: We have evaluated the feasibility of using a mathematical model of glucose disappearance to estimate insulin sensitivity. Glucose was injected into conscious dogs at 100, 200, or 300 mg/kg. The measured time course of insulin was regarded as the "input," and the falling glucose concentration as the "output" of the physiological system storing and using glucose. Seven mathematical models of glucose uptake were compared to identify the representation most capable of simulating glucose disappearance. One specific nonlinear model was superior in that it 1) predicted the time course of glucose after glucose injection, 2) had four parameters that could be precisely estimated, and 3) described individual experiments with similar parameter values. Insulin sensitivity index (SI), defined as the dependence of fractional glucose disappearance on plasma insulin, was the ratio of two parameters of the chosen model and could be estimated with good reproducibility from the 300 mg/kg injection experiments (SI = 7.00 X 10(-4) +/- 24% (coefficient of variation) min-1/(microU/ml) (n = 8)). Thus, from a single glucose injection it is possible to obtain a quantitative index of insulin sensitivity that may have clinical applicability.
1,878 citations
TL;DR: Emerging evidence supports the potentially unifying hypothesis that both of these prominent features of type 2 diabetes are caused by mitochondrial dysfunction.
Abstract: Maintenance of normal blood glucose levels depends on a complex interplay between the insulin responsiveness of skeletal muscle and liver and glucose-stimulated insulin secretion by pancreatic β cells. Defects in the former are responsible for insulin resistance, and defects in the latter are responsible for progression to hyperglycemia. Emerging evidence supports the potentially unifying hypothesis that both of these prominent features of type 2 diabetes are caused by mitochondrial dysfunction.
1,868 citations