scholarly journals Insulin and Insulin Receptors in Adipose Tissue Development

2019 ◽  
Vol 20 (3) ◽  
pp. 759 ◽  
Author(s):  
Angelo Cignarelli ◽  
Valentina Genchi ◽  
Sebastio Perrini ◽  
Annalisa Natalicchio ◽  
Luigi Laviola ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Insulin Receptor ◽  
Intracellular Signaling ◽  
Insulin Receptors ◽  
Metabolic Effects ◽  
Endocrine Activity ◽  
Differentiated Cells ◽  
And Function

Insulin is a major endocrine hormone also involved in the regulation of energy and lipid metabolism via the activation of an intracellular signaling cascade involving the insulin receptor (INSR), insulin receptor substrate (IRS) proteins, phosphoinositol 3-kinase (PI3K) and protein kinase B (AKT). Specifically, insulin regulates several aspects of the development and function of adipose tissue and stimulates the differentiation program of adipose cells. Insulin can activate its responses in adipose tissue through two INSR splicing variants: INSR-A, which is predominantly expressed in mesenchymal and less-differentiated cells and mainly linked to cell proliferation, and INSR-B, which is more expressed in terminally differentiated cells and coupled to metabolic effects. Recent findings have revealed that different distributions of INSR and an altered INSR-A:INSR-B ratio may contribute to metabolic abnormalities during the onset of insulin resistance and the progression to type 2 diabetes. In this review, we discuss the role of insulin and the INSR in the development and endocrine activity of adipose tissue and the pharmacological implications for the management of obesity and type 2 diabetes.

scholarly journals Molecular docking analysis of compounds from Lycopersicon esculentum with the insulin receptor to combat type 2 diabetes

2020 ◽  
Vol 16 (10) ◽  
pp. 748-752
Author(s):  
Anitha Roy ◽  
Keyword(s):  
Type 2 Diabetes ◽  
Molecular Docking ◽  
Lycopersicon Esculentum ◽  
Insulin Receptor ◽  
Bioactive Compounds ◽  
Insulin Receptors ◽  
Docking Analysis ◽  
Molecular Docking Analysis

It is known that tomato (Lycopersicon esculentum) contains bioactive compounds to combat type-2 diabetes. Therefore, it is of interest to document data from the molecular docking analysis of compounds from Lycopersicon esculentum with the insulin receptors to combat type-2 diabetes. We report the binding features of cinnamicacid, chlorogenicacid, gallicacid & glucoside with insulin receptors for further consideration.

Insulin receptor function is preserved in a physiological state of hypoinsulinemia and insulin resistance

1992 ◽  
Vol 262 (6) ◽  
pp. E818-E825
Author(s):  
J. Maury ◽  
A. F. Burnol ◽  
M. Loizeau ◽  
T. Issad ◽  
J. Girard ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Receptor ◽  
Physiological State ◽  
Insulin Receptors ◽  
Partial Purification ◽  
Suckling Period ◽  
Plasma Insulin Concentration ◽  
Receptor Number ◽  
And Function

The suckling period in the rat is characterized by a continuously low plasma insulin concentration and a physiological insulin resistance, particularly in the adipose tissue. This insulin resistance disappears after weaning on the high-carbohydrate adult diet. We have studied the number, structure, and function of adipose tissue insulin receptors during the suckling-weaning transition. The insulin receptor number determined either on intact adipocytes or after partial purification was higher during suckling (15 days), whereas the affinity was similar when compared with weaned rats (30 days). The molecular weight of the alpha- and beta-subunits were identical in both groups and, when analyzed in nonreducing conditions, the alpha 2 beta 2-form was the unique detectable form of the receptor. Neither the basal and insulin-stimulated autophosphorylation of the insulin receptor beta-subunit nor the tyrosine kinase activity toward a synthetic substrate was decreased during the suckling period. Thus, in the adipose tissue of the suckling rat, a marked insulin resistance is concomitant with a normal insulin receptor number and function.

scholarly journals Adipose Tissue, Muscle, and Function: Potential Mediators of Associations Between Body Weight and Mortality in Older Adults With Type 2 Diabetes

Diabetes Care ◽  
2014 ◽  
Vol 37 (12) ◽  
pp. 3213-3219 ◽  
Author(s):  
Rachel A. Murphy ◽  
Ilse Reinders ◽  
Melissa E. Garcia ◽  
Gudny Eiriksdottir ◽  
Lenore J. Launer ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Older Adults ◽  
Body Weight ◽  
Adipose Tissue ◽  
And Function ◽  
Function Potential

scholarly journals Genetic Evidence for Different Adiposity Phenotypes and their Opposing Influence on Ectopic Fat and Risk of Cardiometabolic Disease

2021 ◽  
Author(s):  
Susan Martin ◽  
Madeleine Cule ◽  
Nicolas Basty ◽  
Jessica Tyrrell ◽  
Robin N. Beaumont ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Metabolic Profile ◽  
Liver Fat ◽  
Metabolic Effects ◽  
Ectopic Fat ◽  
Alcoholic Fatty Liver ◽  
Cardiometabolic Diseases ◽  
Risk Of Disease

To understand the causal role of adiposity and ectopic fat in type 2 diabetes and cardiometabolic diseases, we aimed to identify two clusters of adiposity genetic variants, one with ‘adverse’ metabolic effects (UFA) and the other with, paradoxically, ‘favourable’ metabolic effects (FA). We performed a multivariate genome-wide association study using body fat percentage and metabolic biomarkers from UK Biobank and identified 38 UFA and 36 FA variants. Adiposity-increasing alleles were associated with an adverse metabolic profile, higher risk of disease, higher CRP, higher fat in subcutaneous and visceral adipose tissue, liver and pancreas for UFA; and a favourable metabolic profile, lower risk of disease, higher CRP, higher subcutaneous adipose tissue but lower liver fat for FA. We detected no sexual dimorphism. The Mendelian randomization studies provided evidence for risk-increasing effect of UFA and protective effect of FA on type 2 diabetes, heart disease, hypertension, stroke, non-alcoholic fatty liver disease and polycystic ovary syndrome. FA is distinct from UFA by its association with lower liver fat, and protection from cardiometabolic diseases; it was not associated with visceral or pancreatic fat. Understanding the difference in FA and UFA may lead to new insights in preventing, predicting and treating of cardiometabolic diseases.

scholarly journals Leptin Improves Insulin Resistance and Hyperglycemia in a Mouse Model of Type 2 Diabetes

Endocrinology ◽  
2005 ◽  
Vol 146 (9) ◽  
pp. 4024-4035 ◽  
Author(s):  
Yuka Toyoshima ◽  
Oksana Gavrilova ◽  
Shoshana Yakar ◽  
William Jou ◽  
Stephanie Pack ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mouse Model ◽  
Insulin Receptors ◽  
Metabolic Effects ◽  
Acid Oxidation ◽  
Primary Defect ◽  
Peripheral Tissues ◽  
Liver And Pancreas ◽  
Insulin Responsiveness

Abstract Leptin has metabolic effects on peripheral tissues including muscle, liver, and pancreas, and it has been successfully used to treat lipodystrophic diabetes, a leptin-deficient state. To study whether leptin therapy can be used for treatment of more common cases of type 2 diabetes, we used a mouse model of type 2 diabetes (MKR mice) that show normal leptin levels and are diabetic due to a primary defect in both IGF-I and insulin receptors signaling in skeletal muscle. Here we show that leptin administration to the MKR mice resulted in improvement of diabetes, an effect that was independent of the reduced food intake. The main effect of leptin therapy was enhanced hepatic insulin responsiveness possibly through decreasing gluconeogenesis. In addition, the reduction of lipid stores in liver and muscle induced by enhancing fatty acid oxidation and inhibiting lipogenesis led to an improvement of the lipotoxic condition. Our data suggest that leptin could be a potent antidiabetic drug in cases of type 2 diabetes that are not leptin resistant.

scholarly journals Vascular and metabolic effects of adrenaline in adipose tissue in type 2 diabetes

2012 ◽  
Vol 2 (9) ◽  
pp. e46-e46 ◽  
Author(s):  
L Tobin ◽  
L Simonsen ◽  
H Galbo ◽  
J Bülow
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Metabolic Effects

scholarly journals Genetic Evidence for Different Adiposity Phenotypes and their Opposing Influence on Ectopic Fat and Risk of Cardiometabolic Disease

2021 ◽  
Author(s):  
Susan Martin ◽  
Madeleine Cule ◽  
Nicolas Basty ◽  
Jessica Tyrrell ◽  
Robin N. Beaumont ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Metabolic Profile ◽  
Liver Fat ◽  
Metabolic Effects ◽  
Ectopic Fat ◽  
Alcoholic Fatty Liver ◽  
Cardiometabolic Diseases ◽  
Risk Of Disease

To understand the causal role of adiposity and ectopic fat in type 2 diabetes and cardiometabolic diseases, we aimed to identify two clusters of adiposity genetic variants, one with ‘adverse’ metabolic effects (UFA) and the other with, paradoxically, ‘favourable’ metabolic effects (FA). We performed a multivariate genome-wide association study using body fat percentage and metabolic biomarkers from UK Biobank and identified 38 UFA and 36 FA variants. Adiposity-increasing alleles were associated with an adverse metabolic profile, higher risk of disease, higher CRP, higher fat in subcutaneous and visceral adipose tissue, liver and pancreas for UFA; and a favourable metabolic profile, lower risk of disease, higher CRP, higher subcutaneous adipose tissue but lower liver fat for FA. We detected no sexual dimorphism. The Mendelian randomization studies provided evidence for risk-increasing effect of UFA and protective effect of FA on type 2 diabetes, heart disease, hypertension, stroke, non-alcoholic fatty liver disease and polycystic ovary syndrome. FA is distinct from UFA by its association with lower liver fat, and protection from cardiometabolic diseases; it was not associated with visceral or pancreatic fat. Understanding the difference in FA and UFA may lead to new insights in preventing, predicting and treating of cardiometabolic diseases.

scholarly journals Knockout Mice Challenge our Concepts of Glucose Homeostasis and the Pathogenesis of Diabetes

2003 ◽  
Vol 4 (3) ◽  
pp. 169-182 ◽  
Author(s):  
C. Ronald Kahn
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Receptor ◽  
Glucose Homeostasis ◽  
Intracellular Signaling ◽  
Insulin Action ◽  
Central Component ◽  
The Metabolic Syndrome

A central component of type 2 diabetes and the metabolic syndrome is insulin resistance. Insulin exerts a multifaceted and highly integrated series of actions via its intracellular signaling systems. Generation of mice carrying null mutations of the genes encoding proteins in the insulin signaling pathway provides a unique approach to determining the role of individual proteins in the molecular mechanism of insulin action and the pathogenesis of insulin resistance and diabetes. The role of the four major insulin receptor substrates (IRS1-4) in insulin and IGF-1 signaling have been examined by creating mice with targeted gene knockouts. Each produces a unique phenotype, indicating the complementary role of these signaling components. Combined heterozygous defects often produce synergistic or epistatic effects, although the final severity of the phenotype depends on the genetic background of the mice. Conditional knockouts of the insulin receptor have also been created using the Cre-lox system. These tissue specific knockouts have provide unique insights into the control of glucose homeostasis and the pathogenesis of type 2 diabetes, and have led to development of new hypotheses about the nature of the insulin action and development of diabetes.

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