Ligand‐induced activation of the insulin receptor: a multi‐step process involving structural changes in both the ligand and the receptor

Ward, Colin W.; Lawrence, Michael C.

doi:10.1002/bies.200800210

Cited by 140 publications

(142 citation statements)

References 99 publications

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“…The mechanism of action of carvedilol in increasing insulin secretion is briefly described herein [12,[22][23][24]. Carvedilol blocks the sympathetic nervous system, SNS, which is very important in insulin resistance and has been studied extensively.…”

Section: Introductionmentioning

confidence: 99%

“…SNS stimulation decreases insulin secretion by the pancreas [15,24,27]. SNS overstimulation causes gluconeogenesis, glycogenolysis, and lipolysis.…”

Section: Introductionmentioning

confidence: 99%

“…The aforementioned actions of the SNS are blocked by carvedilol while improving insulin secretion and blunting the action of glucagon [24,26]. Therefore, carvedilol has two actions on glucagon: decreasing its secretion and blunting its action [26].…”

Section: Introductionmentioning

confidence: 99%

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Carvedilol can Replace Insulin in the Treatment of Type 2 Diabetes Mellitus

Ahmad¹

2017

J Diabetes Metab

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Introduction: A large number of patients with diabetes mellitus do not want to take insulin or any injectable medication. Carvedilol can replace insulin in the treatment of T2 diabetes mellitus. Carvedilol alone or with oral anti-diabetic drugs (OAD) can replace the entire dose of insulin for patients with T2 diabetes (T2D). Carvedilol can replace insulin in patients on OAD who need insulin. Glycemic control was achieved in patients with T2D. This study was based on the hypothesis that carvedilol decreases insulin resistance, eliminates glucotoxicity and lipotoxicty and improves the function of beta-cell while reducing their apotosis.Method: In this study, 48 patients with T2D were treated with carvedilol, which was an "off-label" use of carvedilol, for the treatment of diabetes mellitus. Twenty-nine patients with T2D were on OAD, and nineteen patients were taking insulin. Both groups had high HbA1c. Carvedilol was given with or without OAD to both groups, and glycemic control was achieved. OAD included metformin and/or glimepiride or glyburide and/or sitagliptin.Results: Glycemic control was achieved using carvedilol with or without OAD in both groups. Conclusion:1. Carvedilol can reduce insulin resistance. 2. Carvedilol can replace insulin in patients with diabetes mellitus. 3. Carvedilol and metformin can prevent the progression of pre-diabetes to diabetes. 4. Patients who are on a very high dose of insulin can decrease that dose using carvedilol and metformin.

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Section: Introductionmentioning

confidence: 99%

“…SNS stimulation decreases insulin secretion by the pancreas [15,24,27]. SNS overstimulation causes gluconeogenesis, glycogenolysis, and lipolysis.…”

Section: Introductionmentioning

confidence: 99%

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Carvedilol can Replace Insulin in the Treatment of Type 2 Diabetes Mellitus

Ahmad¹

2017

J Diabetes Metab

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“…Insulin-like growth factor I (IGF-I) can also bind, albeit more weakly, insulin receptor and the structural similarity between insulin receptor and IGF-I receptor makes possible the binding of visfatin with both receptors. 26 Insulin-like growth factor I enhances erythropoiesis, 27,28 and interestingly it plays a key role in regulating erythropoiesis in HD patients with erythrocytosis. 29 Additionally, stimulation of insulin receptor in erythrocytes augments glycolysis and prevents red cell hemolysis.…”

Section: 2mentioning

confidence: 99%

Increased visfatin in hemodialysis patients is associated with decreased demands for recombinant human erythropoietin

et al. 2013

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“…When insulin is attached to insulin receptor of the cell, it initiates a cascade of events that mediates the absorption of glucose from the blood into the cell. 3 Phosphorylase kinase (PhK) is the regulatory enzyme responsible for catalyzing the rate limiting step in glycogen breakdown. PhK activates glycogen phosphorylase resulting in degradation of glycogen to glucose-1-phosphate.…”

Section: Introductionmentioning

confidence: 99%

In silico Docking Studies on ATP-Sensitive K+Channel, Insulin Receptor and Phosphorylase kinase Activity by Isolated Active Principles of Stereospermum tetragonum DC

Kingsley¹,

Kumari²,

Subramoniam³

et al. 2017

JYP

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INTRODUCTIONATP-sensitive potassium (K ATP ) channels play a central role in glucosestimulated insulin secretion from pancreatic beta cells. Insulin secretion is initiated by closure of the channels and inhibited by their opening. 1The beta-cell K ATP channel is an octameric complex of four pore-forming, inwardly rectifying potassium-channel subunits (Kir6.2) and four regulatory sulfonylurea-receptor subunits (SUR1). Both Kir6.2 and SUR1 are required for correct metabolic regulation of the channel: ATP closes the channel by binding to Kir6.2, and magnesium nucleotides (Mg-ADP and Mg-ATP) stimulate channel activity by interacting with SUR1. Sulfonylureas stimulate insulin secretion in type2 diabetes by binding to SUR1 and closing K ATP channels by an ATP-independent mechanism.2 Insulin receptor belongs to the class of tyrosine kinase receptor. The binding of insulin to its receptor causes conformational changes in the receptor leading to the activation of tyrosine kinase beta subunit. Insulin is responsible for phosphorylation of insulin receptor that leads to glucose uptake by the cells. Insulin is secreted by pancreatic islets in response to increase in blood glucose levels. Most cells of the body have insulin receptors which bind the insulin that is present in the blood circulation. When insulin is attached to insulin receptor of the cell, it initiates a cascade of events that mediates the absorption of glucose from the blood into the cell.3 Phosphorylase kinase (PhK) is the regulatory enzyme responsible for catalyzing the rate limiting step in glycogen breakdown. PhK activates glycogen phosphorylase resulting in degradation of glycogen to glucose-1-phosphate. In liver, these reactions allow for the maintenance of blood glucose, and in muscle, they lead to energy production to sustain muscle contraction. It is comprised of four different subunits with a stoichiometry of (α,β, γ, δ).α,β, and δ are regulatory, while γ is catalytic. The α subunit is encoded by two different genes. 4,5 The objective of the present study was to investigate the in silico antidiabetic effects of the isolated compound 1,4a,5,7a-tetrahydro-5-hydroxy-7-(hydroxymethyl) -1 -(tetrahydro-6-(hydroxymethyl) -3,4,5-trimethoxy-2H-pyran-2-yloxy) cyclopenta (c) pyran -4 -carboxylic acid and 5,8-dihydro-7-isopentyl-2,3,5,8-tetramethoxynaphthalene-1,4,6-triol. MATERIALS AND METHODS Collection of plant materialsThe root parts of S. tetragonum (family: Bignoniaceae) was collected from Tirunelveli district of Tamil Nadu, India and identified by the taxonomist of TBGRI and a voucher specimen (TBGRI 8282) has been deposited in the institute herbarium. Aqueous extraction of dry powderTo prepare water extract, the powder S. tetragonum was extracted with distilled water (5 g/100 ml) by stirring for 4 hours and then filtering

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Ligand‐induced activation of the insulin receptor: a multi‐step process involving structural changes in both the ligand and the receptor

Cited by 140 publications

References 99 publications

Carvedilol can Replace Insulin in the Treatment of Type 2 Diabetes Mellitus

Carvedilol can Replace Insulin in the Treatment of Type 2 Diabetes Mellitus

Increased visfatin in hemodialysis patients is associated with decreased demands for recombinant human erythropoietin

In silico Docking Studies on ATP-Sensitive K+Channel, Insulin Receptor and Phosphorylase kinase Activity by Isolated Active Principles of Stereospermum tetragonum DC

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