Receptors, Antireceptor Antibodies and Mechanisms of Insulin Resistance

Bleich, Howard L.; Boro, Emily S.; Flier, Jeffrey S.; Kahn, C. Ronald; Roth, Jesse

doi:10.1056/nejm197902223000808

Cited by 163 publications

(14 citation statements)

References 30 publications

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“…The cellular mechanisms for insulin resistance have been reviewed extensively (Flier et al, 1979; Holland and Summers, 2008; Shulman, 2004). A substantial emphasis on mechanisms underlying insulin resistance in liver and skeletal muscle has been placed on the roles of impaired mitochondrial fatty acid oxidation and excess accumulation of lipid metabolites diacylglycerol and ceramides.…”

Section: Skeletal Muscle Insulin Resistance and Fatty Acid Metabolismmentioning

confidence: 99%

Metabolic Flexibility in Health and Disease

2017

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Summary Metabolic flexibility is the ability to respond or adapt to conditional changes in metabolic demand. This broad concept has been propagated to explain insulin resistance and mechanisms governing fuel selection between glucose and fatty acids, highlighting the metabolic inflexibility of obesity and type 2 diabetes. In parallel, contemporary exercise physiology research has helped to identify potential mechanisms underlying altered fuel metabolism in obesity and diabetes. Advances in ‘omics’ technologies have further stimulated additional basic and clinical-translational research to further interrogate mechanisms for improved metabolic flexibility in skeletal muscle and adipose tissue with the goal to prevent and treat metabolic disease.

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Section: Skeletal Muscle Insulin Resistance and Fatty Acid Metabolismmentioning

confidence: 99%

Metabolic Flexibility in Health and Disease

2017

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“…Another group of 20 healthy females matched with patients for age were included and served as control. After 12 hrs fasting, blood samples (10 ml) were obtained from each patient for the evaluation of FPG, HbA1c, leptin and insulin levels at zero time and after three months of treatment using standard methods [13][14][15][16]. Plasma levels of metformin were analyzed by HPLC method [17,18].…”

Section: Methodsmentioning

confidence: 99%

Dose-dependent relationship between serum metformin levels and glycemic control, insulin resistance and leptin levels in females newly diagnosed with type 2 diabetes mellitus

Kadhim¹,

Ismael²,

Khalaf³

et al. 2012

JDM

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Despite the extensive clinical experience with the use of metformin worldwide, no formal doseranging study has been conducted because the current dosing strategy of metformin was determined empirically, rather than by an understanding of its dose-response relationship in patients with type 2 diabetes. The present study was designed to evaluate the correlation between serum metformin levels and glycemic control, insulin resistance and leptin levels in females newly diagnosed with type 2 diabetes. Sixty type 2 diabetic females were recruited for the study and were allocated into 3 groups; each receiving metformin 1000, 1500 and 2000 mg/day respectively for 3 months. Blood samples withdrawn from each patient at zero time and after 3 months is used to evaluate serum levels of HbA1c, glucose, leptin and insulin, in addition, the measurement of serum level of metformin in blood after 3 months by HPLC. The results demonstrated that all the treated groups with different doses of metformin showed significant improve in all parameters; the use of increased metformin doses was only correlated with plasma leptin levels in the highest dose. In conclusion, serum metformin levels are not good predictors for correlating improvement in clinical and biochemical parameters with increasing the dose in newly diagnosed non-insulin resistant females with type 2 diabetes.

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“…Unlike FGF21 itself, the antibodies described by Wu et al are specific to FGFR1 and function independent of βKlotho (1). As with agonistic anti-insulin receptor antibodies (3), these antibodies work by facilitating homo-dimerization and activation of these receptors (1). Since FGFR1 is most highly expressed in adipose tissue, especially brown adipose tissue, and minimally expressed in liver, stimulation by the anti-receptor antibody distinguishes the contribution of these tissues to the metabolic effects of FGF21/FGFR1 signaling.…”

Section: Fgf21 and Brown Fat As Potential Targets For Therapy Of Diabmentioning

confidence: 99%

“…But it was the discovery of stimulatory autoantibodies directed at the TSH receptor in Graves’ disease (originally termed long-acting thyroid stimulator or LATS and now termed anti-TSH receptor antibodies or TRAbs) which led to the recognition that antibodies to cell surface receptors could alter their function and mimic hormone action (2). Since then multiple surface proteins have been identified as targets of autoantibodies in endocrine and neurological diseases (3). In some cases, as with LATS, these antibodies produce stimulatory effects, but in most cases, these anti-receptor antibodies inhibit receptor binding and/or signaling, as first shown for antibodies to the acetylcholine receptor in myasthenia gravis (4).…”

mentioning

confidence: 99%

“…In some cases, as with LATS, these antibodies produce stimulatory effects, but in most cases, these anti-receptor antibodies inhibit receptor binding and/or signaling, as first shown for antibodies to the acetylcholine receptor in myasthenia gravis (4). Autoantibodies to the insulin receptor can be either inhibitory, creating severe insulin-resistant diabetes, or stimulatory, resulting in hypoglycemia, in different individuals at different phases of the disease (3). …”

mentioning

confidence: 99%

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