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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: Evidence that genetic and environmental factors can lead to hyperglycemia, dyslipidemia, inflammation, and autoimmunity, resulting in β-cell dysfunction, thereby triggering the pathogenesis of diabetes is presented.
Abstract: Pancreatic β-cell dysfunction plays an important role in the pathogenesis of both type 1 and type 2 diabetes. Insulin, which is produced in β-cells, is a critical regulator of metabolism. Insulin is synthesized as preproinsulin and processed to proinsulin. Proinsulin is then converted to insulin and C-peptide and stored in secretary granules awaiting release on demand. Insulin synthesis is regulated at both the transcriptional and translational level. The cis-acting sequences within the 5' flanking region and trans-activators including paired box gene 6 (PAX6), pancreatic and duodenal homeobox- 1(PDX-1), MafA, and β-2/Neurogenic differentiation 1 (NeuroD1) regulate insulin transcription, while the stability of preproinsulin mRNA and its untranslated regions control protein translation. Insulin secretion involves a sequence of events in β-cells that lead to fusion of secretory granules with the plasma membrane. Insulin is secreted primarily in response to glucose, while other nutrients such as free fatty acids and amino acids can augment glucose-induced insulin secretion. In addition, various hormones, such as melatonin, estrogen, leptin, growth hormone, and glucagon like peptide-1 also regulate insulin secretion. Thus, the β-cell is a metabolic hub in the body, connecting nutrient metabolism and the endocrine system. Although an increase in intracellular [Ca2+] is the primary insulin secretary signal, cAMP signaling- dependent mechanisms are also critical in the regulation of insulin secretion. This article reviews current knowledge on how β-cells synthesize and secrete insulin. In addition, this review presents evidence that genetic and environmental factors can lead to hyperglycemia, dyslipidemia, inflammation, and autoimmunity, resulting in β-cell dysfunction, thereby triggering the pathogenesis of diabetes.

712 citations

Journal ArticleDOI
Guenther Boden1
TL;DR: The challenges for the future include the prevention or correction of obesity and elevated plasma FFA levels through methods that include decreased caloric intake and increased caloric expenditure, the development of methods to measure FFAs in small blood samples, and the developmentof efficient pharmacologic approaches to normalize increased plasma F FA levels.

711 citations

Journal ArticleDOI
TL;DR: It is shown that p53 expression in adipose tissue is crucially involved in the development of insulin resistance, which underlies age-related cardiovascular and metabolic disorders and suggests that cellular aging signals in adipOSE tissue could be a new target for the treatment of diabetes.
Abstract: A role for cell senescence and p53 in the development of insulin resistance (or prediabetes) has been obscure. Issei Komuro and colleagues now show that premature cell senescence occurs in the adipose tissue of obese mice and humans and that genetic deficiency of p53 is sufficient to prevent insulin resistance in mouse models of obesity, suggesting a new target to treat diabetes. Various stimuli, such as telomere dysfunction and oxidative stress, can induce irreversible cell growth arrest, which is termed 'cellular senescence'1,2. This response is controlled by tumor suppressor proteins such as p53 and pRb. There is also evidence that senescent cells promote changes related to aging or age-related diseases3,4,5,6. Here we show that p53 expression in adipose tissue is crucially involved in the development of insulin resistance, which underlies age-related cardiovascular and metabolic disorders. We found that excessive calorie intake led to the accumulation of oxidative stress in the adipose tissue of mice with type 2 diabetes–like disease and promoted senescence-like changes, such as increased activity of senescence-associated β-galactosidase, increased expression of p53 and increased production of proinflammatory cytokines. Inhibition of p53 activity in adipose tissue markedly ameliorated these senescence-like changes, decreased the expression of proinflammatory cytokines and improved insulin resistance in mice with type 2 diabetes–like disease. Conversely, upregulation of p53 in adipose tissue caused an inflammatory response that led to insulin resistance. Adipose tissue from individuals with diabetes also showed senescence-like features. Our results show a previously unappreciated role of adipose tissue p53 expression in the regulation of insulin resistance and suggest that cellular aging signals in adipose tissue could be a new target for the treatment of diabetes ( pages 996–967 ).

710 citations

Journal ArticleDOI
15 Aug 1980-Science
TL;DR: An important role for vitamin D in the endocrine functioning of the pancreas is indicated by the previously demonstrated presence of a vitamin D-dependent calcium-binding protein and cytosol receptor for the hormonal form of vitamin D, 1,25-dihydroxyvitamin D3.
Abstract: The effects of a vitamin D deficiency on insulin and glucagon release was determined in the isolated perfused rat pancreas by radioimmunoassay of the secreted proteins. During a 30-minute period of perfusion with glucose and arginine, pancreases from vitamin D-deficient rats exhibited a 48 percent reduction in insulin secretion compared to that for pancreases from vitamin D-deficient rats that had been replenished with vitamin D. Vitamin D status had no effect on pancreatic glucagon secretion. This result, along with the previously demonstrated presence in the pancreas of a vitamin D-dependent calcium-binding protein and cytosol receptor for the hormonal form of vitamin D, 1,25-dihydroxyvitamin D3, indicates an important role for vitamin D in the endocrine functioning of the pancreas.

709 citations

Journal ArticleDOI
TL;DR: The distinct metabolic features present in subjects with IFG and IGT may require different therapeutic interventions to prevent their progression to type 2 diabetes.
Abstract: Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) are intermediate states in glucose metabolism that exist between normal glucose tolerance and overt diabetes. Epidemiological studies demonstrate that the two categories describe distinct populations with only partial overlap, suggesting that different metabolic abnormalities characterize IGT and IFG. Insulin resistance and impaired β-cell function, the primary defects observed in type 2 diabetes, both can be detected in subjects with IGT and IFG. However, clinical studies suggest that the site of insulin resistance varies between the two disorders. While subjects with IGT have marked muscle insulin resistance with only mild hepatic insulin resistance, subjects with IFG have severe hepatic insulin resistance with normal or near-normal muscle insulin sensitivity. Both IFG and IGT are characterized by a reduction in early-phase insulin secretion, while subjects with IGT also have impaired late-phase insulin secretion. The distinct metabolic features present in subjects with IFG and IGT may require different therapeutic interventions to prevent their progression to type 2 diabetes.

709 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