The Impact of Insulin Resistance on Cardiovascular Control during Exercise in Diabetes

Pregnancy hypertensive disorders such as Preeclampsia (PE) are strongly correlated with insulin resistance, a condition in which the metabolic handling of D-glucose is deficient. In addition, the impact of preeclampsia is enhanced by other insulin-resistant disorders, including polycystic ovary syndrome and obesity. For this reason, there is a clear association between maternal insulin resistance, polycystic ovary syndrome, obesity and the development of PE. However, whether PE is a consequence or the cause of these disorders is still unclear. Insulin therapy is usually recommended to pregnant women with diabetes mellitus when dietary and lifestyle measures have failed. The advantage of insulin therapy for Gestational Diabetes Mellitus (GDM) patients with hypertension is still controversial; surprisingly, there are no studies in which insulin therapy has been used in patients with hypertension in pregnancy without or with an established GDM. This review is focused on the use of insulin therapy in hypertensive disorders in the pregnancy and its effect on offspring and mother later in life. PubMed and relevant medical databases have been screened for literature covering research in the field especially in the last 5-10 years.

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The Impact of Differentiation on Cytotoxicity and Insulin Sensitivity in Streptozotocin Treated SH-SY5Y Cells

Neurochemical Research ◽

10.1007/s11064-021-03269-2 ◽

2021 ◽

Vol 46 (6) ◽

pp. 1350-1358

Author(s):

Fruzsina Bagaméry ◽

Kamilla Varga ◽

Kitti Kecsmár ◽

István Vincze ◽

Éva Szökő ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Insulin Signaling ◽

Glycogen Synthase ◽

Insulin Metabolism ◽

Relative Significance ◽

Differentiated Cells ◽

Mature Neuron ◽

The Right ◽

The Impact

AbstractRecently neuronal insulin resistance was suggested playing a role in Alzheimer’s disease. Streptozotocin (STZ) is commonly used to induce impairment in insulin metabolism. In our previous work on undifferentiated SH-SY5Y cells the compound exerted cytotoxicity without altering insulin sensitivity. Nevertheless, differentiation of the cells to a more mature neuron-like phenotype may considerably affect the significance of insulin signaling and its sensitivity to STZ. We aimed at studying the influence of STZ treatment on insulin signaling in SH-SY5Y cells differentiated by retinoic acid (RA). Cytotoxicity of STZ or low serum (LS) condition and protective effect of insulin were compared in RA differentiated SH-SY5Y cells. The effect of insulin and an incretin analogue, exendin-4 on insulin signaling was also examined by assessing glycogen synthase kinase-3 (GSK-3) phosphorylation. STZ was found less cytotoxic in the differentiated cells compared to our previous results in undifferentiated SH-SY5Y cells. The cytoprotective concentration of insulin was similar in the STZ and LS groups. However, the right-shifted concentration–response curve of insulin induced GSK-3 phosphorylation in STZ-treated differentiated cells is suggestive of the development of insulin resistance that was further confirmed by the insulin potentiating effect of exendin-4. Differentiation reduced the sensitivity of SH-SY5Y cells for the non-specific cytotoxicity of STZ and enhanced the relative significance of development of insulin resistance. The differentiated cells thus serve as a better model for studying the role of insulin signaling in neuronal survival. However, direct cytotoxicity of STZ also contributes to the cell death.

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Inflammatory Mediators and Insulin Resistance in Obesity: Role of Nuclear Receptor Signaling in Macrophages

Mediators of Inflammation ◽

10.1155/2010/219583 ◽

2010 ◽

Vol 2010 ◽

pp. 1-10 ◽

Cited By ~ 51

Author(s):

Lucía Fuentes ◽

Tamás Rőszer ◽

Mercedes Ricote

Keyword(s):

Insulin Resistance ◽

Nuclear Receptor ◽

Cytokine Production ◽

Current Knowledge ◽

Liver Steatosis ◽

Visceral Obesity ◽

M2 Macrophage ◽

Low Grade ◽

The Impact

Visceral obesity is coupled to a general low-grade chronic inflammatory state characterized by macrophage activation and inflammatory cytokine production, leading to insulin resistance (IR). The balance between proinflammatory M1 and antiinflammatory M2 macrophage phenotypes within visceral adipose tissue appears to be crucially involved in the development of obesity-associated IR and consequent metabolic abnormalities. The ligand-dependent transcription factors peroxisome proliferator activated receptors (PPARs) have recently been implicated in the determination of the M1/M2 phenotype. Liver X receptors (LXRs), which form another subgroup of the nuclear receptor superfamily, are also important regulators of proinflammatory cytokine production in macrophages. Disregulation of macrophage-mediated inflammation by PPARs and LXRs therefore underlies the development of IR. This review summarizes the role of PPAR and LXR signaling in macrophages and current knowledge about the impact of these actions in the manifestation of IR and obesity comorbidities such as liver steatosis and diabetic osteopenia.

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Impact of Glucose Metabolism Disorders on IGF-1 Levels in Patients with Acromegaly

Hormone and Metabolic Research ◽

10.1055/a-0594-2404 ◽

2018 ◽

Vol 50 (05) ◽

pp. 408-413 ◽

Cited By ~ 1

Author(s):

Sema Dogansen ◽

Gulsah Yalin ◽

Seher Tanrikulu ◽

Sema Yarman

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Glucose Metabolism ◽

Glucose Tolerance ◽

Normal Glucose Tolerance ◽

Glucose Metabolism Disorders ◽

Insulin Resistant ◽

Normal Glucose ◽

Resistant Group ◽

The Impact

AbstractIn this study, we aimed to evaluate the presence of glucose metabolism abnormalities and their impact on IGF-1 levels in patients with acromegaly. Ninety-three patients with acromegaly (n=93; 52 males/41 females) were included in this study. Patients were separated into three groups such as; normal glucose tolerance (n=23, 25%), prediabetes (n=38, 41%), and diabetes mellitus (n=32, 34%). Insulin resistance was calculated with homeostasis model assessment (HOMA). HOMA-IR > 2.5 or ≤2.5 were defined as insulin resistant or noninsulin resistant groups, respectively. Groups were compared in terms of factors that may be associated with glucose metabolism abnormalities. IGF-1% ULN (upper limit of normal)/GH ratios were used to evaluate the impact of glucose metabolism abnormalities on IGF-1 levels. Patients with diabetes mellitus were significantly older with an increased frequency of hypertension (p<0.001, p=0.01, respectively). IGF-1% ULN/GH ratio was significantly lower in prediabetes group than in normal glucose tolerance group (p=0.04). Similarly IGF-1% ULN/GH ratio was significantly lower in insulin resistant group than in noninsulin resistant group (p=0.04). Baseline and suppressed GH levels were significantly higher in insulin resistant group than in noninsulin resistant group (p=0.024, p<0.001, respectively). IGF-1% ULN/GH ratio is a useful marker indicating glucose metabolism disorders and IGF-1 levels might be inappropriately lower in acromegalic patients with insulin resistance or prediabetes. We suggest that IGF-1 levels should be re-evaluated after the improvement of insulin resistance or glycemic regulation for the successful management of patients with acromegaly.

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The Impact of Exercise Training Compared to Caloric Restriction on Hepatic and Peripheral Insulin Resistance in Obesity

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2008-2033 ◽

2009 ◽

Vol 94 (11) ◽

pp. 4258-4266 ◽

Cited By ~ 59

Author(s):

Robert H. Coker ◽

Rick H. Williams ◽

Sophie E. Yeo ◽

Patrick M. Kortebein ◽

Don L. Bodenner ◽

...

Keyword(s):

Insulin Resistance ◽

Exercise Training ◽

Caloric Restriction ◽

Peripheral Insulin Resistance ◽

The Impact

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Insulin Resistance as a Predictor of Cardiovascular Disease in Patients on peritoneal dialysis

Peritoneal Dialysis International ◽

10.3747/pdi.2012.00037 ◽

2013 ◽

Vol 33 (4) ◽

pp. 411-418 ◽

Cited By ~ 21

Author(s):

Yun Li ◽

Lihua Zhang ◽

Yong Gu ◽

Chuanming Hao ◽

Tongying Zhu

Keyword(s):

Insulin Resistance ◽

Peritoneal Dialysis ◽

Independent Predictor ◽

Hazard Ratio ◽

Diabetic Patients ◽

Model Assessment ◽

Mortality Hazard ◽

Cv Disease ◽

The Impact ◽

Mortality Hazard Ratio

BackgroundInsulin resistance is associated with multiple risk factors for cardiovascular (CV) disease in the general population. Patients on peritoneal dialysis (PD) are more likely to develop insulin resistance. However, no evaluation of the impact of insulin resistance on CV disease morbidity or mortality in patients on PD has been performed.MethodsOur prospective cohort study included all non-diabetic patients on PD at our center ( n = 66). Insulin resistance was evaluated at baseline by the homeostasis model assessment method (HOMA-IR) using fasting glucose and insulin levels. The cohort was followed for up to 58 months (median: 41.3 months; interquartile range: 34.3 months). A multivariate Cox model was used to analyze the impact of insulin resistance on CV disease mortality.ResultsFourteen CV events occurred in the higher HOMA-IR group [IR-H (HOMA-IR values in the range 2.85 – 19.5), n = 33], but only one event occurred in the lower HOMA-IR group (IR-L (HOMA-IR values in the range 0.83 – 2.71), n = 33) during the follow-up period. Level of HOMA-IR was a significant predictor of CV events [risk ratio: 17.7; 95% confidence interval (CI): 2.10 to 149.5; p = 0.008]. In the IR-H group, 10 patients died (8 CV events), but in the IR-L group, only 4 patients died (1 CV event). Patients in the IR-H group experienced significantly higher CV mortality (hazard ratio: 9.02; 95% CI: 1.13 to 72.2; p = 0.04). Even after adjustments for age, systolic blood pressure, body mass index, C-reactive protein, triglycerides, resistin, and leptin, HOMA-IR remained an independent predictor of CV mortality (hazard ratio: 14.8; 95% CI: 1.22 to 179.1; p = 0.03).ConclusionsInsulin resistance assessed using HOMA-IR was an independent predictor of CV morbidity and mortality in a cohort of nondiabetic patients on PD. Insulin resistance is a modifiable risk factor; the reduction of insulin resistance may reduce CV risk and improve survival in this group of patients.

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Developmental androgen excess programs sympathetic tone and adipose tissue dysfunction and predisposes to a cardiometabolic syndrome in female mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00620.2012 ◽

2013 ◽

Vol 304 (12) ◽

pp. E1321-E1330 ◽

Cited By ~ 38

Author(s):

Kazunari Nohara ◽

Rizwana S. Waraich ◽

Suhuan Liu ◽

Mathieu Ferron ◽

Aurélie Waget ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Glucose Intolerance ◽

Adult Female ◽

Sympathetic Tone ◽

Visceral Adiposity ◽

Androgen Excess ◽

Altered Expression ◽

Female Mice ◽

The Impact

Among women, the polycystic ovarian syndrome (PCOS) is considered a form of metabolic syndrome with reproductive abnormalities. Women with PCOS show increased sympathetic tone, visceral adiposity with enlarged adipocytes, hypoadiponectinemia, insulin resistance, glucose intolerance, increased inactive osteocalcin, and hypertension. Excess fetal exposure to androgens has been hypothesized to play a role in the pathogenesis of PCOS. Previously, we showed that neonatal exposure to the androgen testosterone (NT) programs leptin resistance in adult female mice. Here, we studied the impact of NT on lean and adipose tissues, sympathetic tone in cardiometabolic tissues, and the development of metabolic dysfunction in mice. Neonatally androgenized adult female mice (NTF) displayed masculinization of lean tissues with increased cardiac and skeletal muscle as well as kidney masses. NTF mice showed increased and dysfunctional white adipose tissue with increased sympathetic tone in both visceral and subcutaneous fat as well as increased number of enlarged and insulin-resistant adipocytes that displayed altered expression of developmental genes and hypoadiponectinemia. NTF exhibited dysfunctional brown adipose tissue with increased mass and decreased energy expenditure. They also displayed decreased undercarboxylated and active osteocalcin and were predisposed to obesity during chronic androgen excess. NTF showed increased renal sympathetic tone associated with increased blood pressure, and they developed glucose intolerance and insulin resistance. Thus, developmental exposure to testosterone in female mice programs features of cardiometabolic dysfunction, as can be observed in women with PCOS, including increased sympathetic tone, visceral adiposity, insulin resistance, prediabetes, and hypertension.

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Impact of disease activity on impaired glucose metabolism in patients with rheumatoid arthritis

Arthritis Research & Therapy ◽

10.1186/s13075-021-02476-0 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Gorica G. Ristić ◽

Vesna Subota ◽

Dejana Stanisavljević ◽

Danilo Vojvodić ◽

Arsen D. Ristić ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Risk Factors ◽

Insulin Resistance ◽

Glucose Metabolism ◽

Disease Activity ◽

Impaired Glucose Metabolism ◽

Inflammation Markers ◽

C Peptide ◽

Related Risk ◽

The Impact

Abstract Objective To explore glucose metabolism in rheumatoid arthritis (RA) and its association with insulin resistance (IR) risk factors and disease activity indicators, including matrix metalloproteinase-3 (MMP3). Methods This single-center study included 127 non-diabetic subjects: 90 RA patients and 37 matched controls. IR-related risk factors, disease activity (DAS28-ESR/CRP), concentrations of inflammation markers, MMP3, glucose, specific insulin, and C-peptide (a marker of β-cell secretion) were determined. Homeostasis Model Assessment was used to establish insulin resistance (HOMA2-IR) and sensitivity (HOMA2-%S). Associations of HOMA2 indices with IR-related risk factors, inflammation markers, and RA activity were tested using multiple regression analyses. Results RA patients had significantly increased HOMA2-IR index than controls. In the RA group, multivariate analysis revealed DAS28-ESR, DAS28-CRP, tender joint counts, patient’s global assessment, and MMP3 level as significant positive predictors for HOMA2-IR (β = 0.206, P = 0.014; β = 0.192, P = 0.009; β = 0.121, P = 0.005; β = 0.148, P = 0.007; β = 0.075, P = 0.025, respectively), and reciprocal negative for HOMA2-%S index. According to the value of the coefficient of determination (R2), DAS28-ESR ≥ 5.1 has the largest proportion of variation in both HOMA2-IR indices. DAS28-ESR ≥ 5.1 and ESR were independent predictors for increased C-peptide concentration (β = 0.090, P = 0.022; β = 0.133, P = 0.022). Despite comparability regarding all IR-related risk factors, patients with DAS28-ESR ≥ 5.1 had higher HOMA2-IR than controls [1.7 (1.2–2.5) vs. 1.2 (0.8–1.4), P = 0.000]. There was no difference between patients with DAS28-ESR < 5.1 and controls [1.3 (0.9–1.9) vs. 1.2 (0.8–1.4), P = 0.375]. Conclusions RA activity is an independent risk factor for impaired glucose metabolism. DAS28-ESR ≥ 5.1 was the main contributor to this metabolic disturbance, followed by MMP3 concentration, outweighing the impact of classic IR-related risk factors.

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Insulin resistance induced by long-term sleep deprivation in rhesus macaques can be attenuated by Bifidobacterium

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00329.2021 ◽

2021 ◽

Author(s):

Ying Zhao ◽

Yan Shu ◽

Ning Zhao ◽

Zili Zhou ◽

Xiong Jia ◽

...

Keyword(s):

Insulin Resistance ◽

Circadian Rhythm ◽

Blood Glucose ◽

Glucose Metabolism ◽

Sleep Deprivation ◽

Rhesus Macaques ◽

Intravenous Glucose ◽

Increased Risk ◽

The Impact

Long-term sleep deprivation (SD) is a bad lifestyle habit, especially among specific occupational practitioners, characterized by circadian rhythm misalignment and abnormal sleep/wake cycles. SD is closely associated with an increased risk of metabolic disturbance, particularly obesity and insulin resistance. The incretin hormone, glucagon-like peptide-1 (GLP-1), is a critical insulin release determinant secreted by the intestinal L-cell upon food intake. Besides, the gut microbiota participates in metabolic homeostasis and regulates GLP-1 release in a circadian rhythm manner. As a commonly recognized intestinal probiotic, Bifidobacterium has various clinical indications regarding its curative effect. However, few studies have investigated the effect of Bifidobacterium supplementation on sleep disorders. In the present study, we explored the impact of long-term SD on the endocrine metabolism of rhesus monkeys and determined the effect of Bifidobacterium supplementation on the SD-induced metabolic status. Lipids concentrations, body weight, fast blood glucose, and insulin levels increased after SD. Furthermore, after two months of long-term SD, the intravenous glucose tolerance test (iVGTT) showed that the glucose metabolism was impaired and the insulin sensitivity decreased. Moreover, one month of Bifidobacterium oral administration significantly reduced blood glucose and attenuated insulin resistance in rhesus macaques. Overall, our results suggested that Bifidobacterium might be used to alleviate SD-induced aberrant glucose metabolism and improve insulin resistance. Also, it might help in better understanding the mechanisms governing the beneficial effects of Bifidobacterium.

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