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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.


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Journal ArticleDOI
TL;DR: The cellular and molecular origins and significance of ROS production, the molecular targets and responses describing how oxidative stress affects cell function including mechanisms of insulin secretion and action are reviewed from the point of view of possible application of novel diabetic therapies based on redox regulation.
Abstract: Oxidative stress and chronic inflammation are known to be associated with the development of metabolic diseases, including diabetes. Oxidative stress, an imbalance between oxidative and antioxidative systems of cells and tissues, is a result of over production of oxidative-free radicals and associated reactive oxygen species (ROS). One outcome of excessive levels of ROS is the modification of the structure and function of cellular proteins and lipids, leading to cellular dysfunction including impaired energy metabolism, altered cell signalling and cell cycle control, impaired cell transport mechanisms and overall dysfunctional biological activity, immune activation and inflammation. Nutritional stress, such as that caused by excess high-fat and/or carbohydrate diets, promotes oxidative stress as evident by increased lipid peroxidation products, protein carbonylation and decreased antioxidant status. In obesity, chronic oxidative stress and associated inflammation are the underlying factors that lead to the development of pathologies such as insulin resistance, dysregulated pathways of metabolism, diabetes and cardiovascular disease through impaired signalling and metabolism resulting in dysfunction to insulin secretion, insulin action and immune responses. However, exercise may counter excessive levels of oxidative stress and thus improve metabolic and inflammatory outcomes. In the present article, we review the cellular and molecular origins and significance of ROS production, the molecular targets and responses describing how oxidative stress affects cell function including mechanisms of insulin secretion and action, from the point of view of possible application of novel diabetic therapies based on redox regulation.

539 citations

Journal ArticleDOI
28 May 2004-Science
TL;DR: A mutation in the gene encoding the protein kinase AKT2/PKBβ in a family that shows autosomal dominant inheritance of severe insulin resistance and diabetes mellitus is described, demonstrating the central importance of AKT signaling to insulin sensitivity in humans.
Abstract: Inherited defects in signaling pathways downstream of the insulin receptor have long been suggested to contribute to human type 2 diabetes mellitus. Here we describe a mutation in the gene encoding the protein kinase AKT2/PKBbeta in a family that shows autosomal dominant inheritance of severe insulin resistance and diabetes mellitus. Expression of the mutant kinase in cultured cells disrupted insulin signaling to metabolic end points and inhibited the function of coexpressed, wild-type AKT. These findings demonstrate the central importance of AKT signaling to insulin sensitivity in humans.

539 citations

Journal ArticleDOI
TL;DR: It is shown that, in the liver, TRB-3 is a target for PPAR-α, a fasting-inducible inhibitor of the serine-threonine kinase Akt/PKB, which indicates a link between nuclear hormone receptor and insulin signaling pathways, and suggest a potential role for TRb-3 inhibitors in the treatment of type 2 diabetes.
Abstract: Insulin resistance is a major hallmark in the development of type 2 diabetes, which is characterized by an impaired ability of insulin to inhibit glucose output from the liver and to promote glucose uptake in muscle. The nuclear hormone receptor coactivator PGC-1 (peroxisome proliferator-activated (PPAR)-gamma coactivator-1) has been implicated in the onset of type 2 diabetes. Hepatic PGC-1 expression is elevated in mouse models of this disease, where it promotes constitutive activation of gluconeogenesis and fatty acid oxidation through its association with the nuclear hormone receptors HNF-4 and PPAR-alpha, respectively. Here we show that PGC-1-deficient mice, generated by adenoviral delivery of PGC-1 RNA interference (RNAi) to the liver, experience fasting hypoglycemia. Hepatic insulin sensitivity was enhanced in PGC-1-deficient mice, reflecting in part the reduced expression of the mammalian tribbles homolog TRB-3, a fasting-inducible inhibitor of the serine-threonine kinase Akt/PKB (ref. 6). We show here that, in the liver, TRB-3 is a target for PPAR-alpha. Knockdown of hepatic TRB-3 expression improved glucose tolerance, whereas hepatic overexpression of TRB-3 reversed the insulin-sensitive phenotype of PGC-1-deficient mice. These results indicate a link between nuclear hormone receptor and insulin signaling pathways, and suggest a potential role for TRB-3 inhibitors in the treatment of type 2 diabetes.

539 citations

Journal ArticleDOI
TL;DR: The effects of agitation rate, interfacial interactions, and insulin concentration on the overall aggregation rate were examined, and mathematical modeling of proposed kinetic schemes was employed to identify possible reaction pathways and to explain greater stability at higher insulin concentration.
Abstract: The stability of protein-based pharmaceuticals (e.g., insulin) is important for their production, storage, and delivery. To gain an understanding of insulin's aggregation mechanism in aqueous solutions, the effects of agitation rate, interfacial interactions, and insulin concentration on the overall aggregation rate were examined. Ultraviolet absorption spectroscopy, high-performance liquid chromatography, and quasielastic light scattering analyses were used to monitor the aggregation reaction and identify intermediate species. The reaction proceeded in two stages; insulin stability was enhanced at higher concentration. Mathematical modeling of proposed kinetic schemes was employed to identify possible reaction pathways and to explain greater stability at higher insulin concentration.

538 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20243
20232,520
20225,252
20213,164
20203,368
20193,376