scholarly journals Conjugated Estrogens and Bazedoxifene Improve β Cell Function in Obese Menopausal Women

2019 ◽  
Vol 3 (8) ◽  
pp. 1583-1594 ◽  
Author(s):  
Dragana Lovre ◽  
Erin Peacock ◽  
Bonnie Katalenich ◽  
Cynthia Moreau ◽  
Beibei Xu ◽  
...  
Keyword(s):  
Body Composition ◽  
Postmenopausal Women ◽  
Glucose Homeostasis ◽  
Cell Function ◽  
Model Assessment ◽  
Β Cell ◽  
Conjugated Estrogens ◽  
Markers Of Inflammation ◽  
Menopausal Women ◽  
Β Cell Function

Abstract Context Studies suggest that menopausal hormone therapy (MHT) prevents type 2 diabetes (T2D). The combination of conjugated estrogens (CE) with the selective estrogen receptor modulator bazedoxifene (BZA) is an MHT that improves obesity and T2D in preclinical models of menopausal metabolic syndrome. The effect of CE/BZA on adiposity and glucose homeostasis in obese postmenopausal women is unknown. Objective To investigate the effect of CE/BZA on body composition, glucose homeostasis, and markers of inflammation in obese postmenopausal women. Research Design, Intervention, and Participants Randomized, double-blind, placebo-controlled pilot trial of 12 obese menopausal women assigned to 12-week treatment with CE 0.45 mg/BZA 20 mg (n = 7) or placebo (n = 5). At baseline and after 12 weeks, we assessed body composition (dual-energy X-ray absorptiometry), glucose homeostasis (IV glucose tolerance test), and inflammation biomarkers. Results Women treated with CE/BZA exhibited increased β cell function using homeostatic model assessment-B [median (interquartile range) CE/BZA vs placebo: 18.5 (−0.9 to 320.6) μU/mM vs −25.5 (−39.9 to −0.1) μU/mM; P = 0.045], and decreased basal glucose concentrations (Gb) [−5.2 (−9.2 to −1.7) mg/dL vs 2.7 (0.9 to 4.9) mg/dL; P = 0.029]. Insulin sensitivity was higher in the placebo arm [1.35 (1.12 to 1.82) (μU/mL) min−1 vs −0.24 (−1.50 to 0.19) (μU/mL) min−1; P = 0.029]. No changes between treatment groups were observed for the acute insulin response to glucose (AIRg), the disposition index (DI), body composition, and inflammatory biomarkers. Conclusions A 12-week treatment of obese postmenopausal women with CEs/BZA improves fasting β cell function and glucose concentrations without change in AIRg, HOMA-IR, DI, body composition, or markers of inflammation.

scholarly journals Leptin Levels, β-Cell Function, and Insulin Sensitivity in Families with Congenital and Acquired Generalized Lipoatropic Diabetes1

1998 ◽  
Vol 83 (2) ◽  
pp. 503-508
Author(s):  
Victor C. Pardini ◽  
Ivana M. N. Victória ◽  
Selma M. V. Rocha ◽  
Danielle G. Andrade ◽  
Aline M. Rocha ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Temporal Relationship ◽  
Cell Function ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Β Cell ◽  
Insulin Levels ◽  
Β Cell Function ◽  
Plasma Leptin ◽  
Specific Insulin

Lipoatropic diabetes (LD) designates a group of syndromes characterized by diabetes mellitus with marked insulin resistance and either a localized or generalized absence of adipose tissue. In this study, we evaluated plasma leptin levels in subjects with congenital generalized lipoatropic diabetes (CGLD, n = 11) or acquired generalized lipoatropic diabetes (AGLD, n = 11), and assessed correlations between leptin levels and estimations of insulin secretion and insulin sensitivity using homeostasis model assessment (HOMA). Leptin levels were 0.86 ± 0.32, 1.76 ± 0.78, and 6.9 ± 4.4 ng/mL in subjects with CGLD, AGLD, and controls (n = 19), respectively (ANOVA P < 0.0001). Specific insulin levels were 154 ± 172, 177 ± 137 and 43 ± 22 pmol/L, respectively (P < 0.0001). Insulin sensitivity was significantly decreased in both groups with LD (P< 0.0001), whereas HOMA β-cell function was not significantly different when compared with controls. Leptin levels were significantly correlated with body mass index, insulin levels, and HOMA β-cell function, and inversely correlated with insulin sensitivity in control subjects but not in subjects with generalized LD. In conclusion, decreased leptin levels were observed in subjects with generalized LD, with a trend towards lower levels in the acquired than in the congenital form (P = 0.06). The temporal relationship between the decrease in leptin levels and the development of lipoatrophy should be investigated in at-risk young relatives of subjects with the acquired forms to assess the usefulness of leptin levels as a marker of lipoatrophy.

scholarly journals Impaired Pancreatic β-Cell Function in Critically Ill Children

2021 ◽  
Vol 9 ◽  
Author(s):  
Shereen A. Mohamed ◽  
Nora E. Badawi ◽  
Hoiyda A. AbdelRasol ◽  
Hossam M. AbdelAziz ◽  
Nirvana A. Khalaf ◽  
...  
Keyword(s):  
Cell Function ◽  
Multivariate Logistic Regression Analysis ◽  
Pediatric Intensive Care ◽  
Glucose Production ◽  
Critically Ill Children ◽  
Model Assessment ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Β Cell Function

Critical illness hyperglycemia (CIH) is common in the pediatric intensive care unit (PICU). Increased glucose production, insulin resistance (IR), and pancreatic β-cell dysfunction are responsible mechanisms. We aimed to investigate β-cell function in the PICU and to uncover its relation to clinical and laboratory variables and ICU mortality. We prospectively recruited 91 children. Pancreatic β-cell function was assessed by using a homeostasis model assessment (HOMA)-β. Patients with β-cell function <40.0% had significantly higher Pediatric Risk of Mortality III (PRISM III) scores, higher rates of a positive C-reactive protein (CRP), lower IR, and a longer hospital stay. The patients with 40–80% β-cell function had the highest IR. Intermediate IR was found when the β-cell function was >80%. ICU survivors had better β-cell function than ICU non-survivors. A multivariate logistic regression analysis revealed that higher PRISM III score and HOMA-β <80.0% were significant predictors of mortality. In conclusion, β-cell dysfunction is prevalent among PICU patients and influences patient morbidity and mortality.

scholarly journals Herbal Medicines Targeting the Improved β-Cell Functions and β-Cell Regeneration for the Management of Diabetes Mellitus

2021 ◽  
Vol 2021 ◽  
pp. 1-32
Author(s):  
Akurange Sujeevi Dammadinna Wickramasinghe ◽  
Pabasara Kalansuriya ◽  
Anoja Priyadarshani Attanayake
Keyword(s):  
Diabetes Mellitus ◽  
Cell Function ◽  
Herbal Medicines ◽  
Cell Regeneration ◽  
Model Assessment ◽  
Β Cells ◽  
Β Cell ◽  
Cell Functions ◽  
Glucose Transporter 2 ◽  
Β Cell Function

There is an increasing trend of investigating natural bioactive compounds targeting pancreatic β-cells for the prevention/treatment of diabetes mellitus (DM). With the exploration of multiple mechanisms by which β-cells involve in the pathogenesis of DM, herbal medicines are gaining attention due to their multitasking ability as evidenced by traditional medicine practices. This review attempts to summarize herbal medicines with the potential for improvement of β-cell functions and regeneration as scientifically proven by in vivo/in vitro investigations. Furthermore, attempts have been made to identify the mechanisms of improving the function and regeneration of β-cells by herbal medicines. Relevant data published from January 2009 to March 2020 were collected by searching electronic databases “PubMed,” “ScienceDirect,” and “Google Scholar” and studied for this review. Single herbal extracts, polyherbal mixtures, and isolated compounds derived from approximately 110 medicinal plants belonging to 51 different plant families had been investigated in recent years and found to be targeting β-cells. Many herbal medicines showed improvement of β-cell function as observed through homeostatic model assessment-β-cell function (HOMA-β). Pancreatic β-cell regeneration as observed in histopathological and immunohistochemical studies in terms of increase of size and number of functional β-cells was also prominent. Increasing β-cell mass via expression of genes/proteins related to antiapoptotic actions and β-cell neogenesis/proliferation, increasing glucose-stimulated insulin secretion via activating glucose transporter-2 (GLUT-2) receptors, and/or increasing intracellular Ca2+ levels were observed upon treatment of some herbal medicines. Some herbal medicines acted on various insulin signaling pathways. Furthermore, many herbal medicines showed protective effects on β-cells via reduction of oxidative stress and inflammation. However, there are many unexplored avenues. Thus, further investigations are warranted in elucidating mechanisms of improving β-cell function and mass by herbal medicines, their structure-activity relationship (SAR), and toxicities of these herbal medicines.

scholarly journals Uric acid lowering improves insulin sensitivity and lowers blood pressure: a meta-analysis of randomized parallel-controlled clinical trials

2021 ◽  
Vol 21 (1) ◽  
pp. 82-95
Author(s):  
Qunchuan Zong ◽  
Guanyi Ma ◽  
Tao Wang
Keyword(s):  
Blood Pressure ◽  
Uric Acid ◽  
Insulin Sensitivity ◽  
Cell Function ◽  
Meta Analysis ◽  
Model Assessment ◽  
Controlled Clinical Trials ◽  
Homeostasis Model Assessment ◽  
Β Cell ◽  
Β Cell Function

Objectives: This meta-analysis aimed to investigate whether uric acid lowering treatment can improve β-cell function and insulin sensitivity. Methods: PubMed, Cochrane Library, EMBASE and China Biology Medicine were searched up to March 1, 2020. Rand- omized controlled clinical trials of urate lowering therapy in hyperuricemia patients were included in meta-analysis. Effect size was estimated as mean difference with 95% confidence interval (CI). Results: Our search yielded 7 eligible trials with 503 participants. This meta-analysis showed that uric acid-lowering thera- py decreased fasting insulin -1.43 μIU/ml (weighted mean differences (WMD, 95% CI -2.78 to -0.09), homeostasis model assessment of insulin resistance -0.65 (WMD, 95% CI -1.05 to -0.24), systolic blood pressure -2.45 mm Hg (WMD, 95%CI -4.57 to -0.33) and diastolic blood pressure -3.41 mm Hg (WMD, 95%CI -3.87 to -2.95). However, the treatment had no significant effect on fasting plasma glucose (WMD -0.19 mmol/L, 95%CI -0.42 to 0.05), homeostasis model assessment of β-cell function index (WMD -0.02, 95%CI -0.28 to 0.24), total cholesterol (WMD 0.18 mg/dl; 95%CI, -1.39 to 1.75) and triglyceride (WMD 3.15 mg/dl, 95% CI -9.83 to 16.14). Conclusion: Uric acid-lowering therapies might improve insulin sensitivity and lower blood pressure, but had no significant effect on HOMA-β and serum lipids. Keywords: Hyperuricemia; uric acid lowering treatment; β-cell function; insulin sensitivity.

scholarly journals VEGF-B ablation in pancreatic β-cells upregulates insulin expression without affecting glucose homeostasis or islet lipid uptake

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Frank Chenfei Ning ◽  
Nina Jensen ◽  
Jiarui Mi ◽  
William Lindström ◽  
Mirela Balan ◽  
...  
Keyword(s):  
Pancreatic Islet ◽  
Glucose Homeostasis ◽  
Lipid Accumulation ◽  
Cell Function ◽  
Lipid Uptake ◽  
Β Cells ◽  
Β Cell ◽  
Peripheral Tissues ◽  
Β Cell Function ◽  
Triglyceride Content

AbstractType 2 diabetes mellitus (T2DM) affects millions of people and is linked with obesity and lipid accumulation in peripheral tissues. Increased lipid handling and lipotoxicity in insulin producing β-cells may contribute to β-cell dysfunction in T2DM. The vascular endothelial growth factor (VEGF)-B regulates uptake and transcytosis of long-chain fatty acids over the endothelium to tissues such as heart and skeletal muscle. Systemic inhibition of VEGF-B signaling prevents tissue lipid accumulation, improves insulin sensitivity and glucose tolerance, as well as reduces pancreatic islet triglyceride content, under T2DM conditions. To date, the role of local VEGF-B signaling in pancreatic islet physiology and in the regulation of fatty acid trans-endothelial transport in pancreatic islet is unknown. To address these questions, we have generated a mouse strain where VEGF-B is selectively depleted in β-cells, and assessed glucose homeostasis, β-cell function and islet lipid content under both normal and high-fat diet feeding conditions. We found that Vegfb was ubiquitously expressed throughout the pancreas, and that β-cell Vegfb deletion resulted in increased insulin gene expression. However, glucose homeostasis and islet lipid uptake remained unaffected by β-cell VEGF-B deficiency.

Circulating Spexin Decreased and Negatively Correlated with Systemic Insulin Sensitivity and Pancreatic β Cell Function in Obese Children

2019 ◽  
Vol 74 (2) ◽  
pp. 125-131 ◽  
Author(s):  
Ting Chen ◽  
Fengyun Wang ◽  
Zhenyu Chu ◽  
Ling Sun ◽  
Haitao Lv ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Insulin Sensitivity ◽  
Cell Function ◽  
Insulinogenic Index ◽  
Model Assessment ◽  
Pancreatic Β Cell ◽  
Obese Children ◽  
Β Cell ◽  
Β Cell Function ◽  
Obese Subjects

Objectives: Spexin (SPX) is a novel peptide that has recently emerged as an important regulatory adipokine of obesity and related metabolic disease. Little is known about its role in children. The aim of the current study was to determine the potential role of SPX in obese children and explore its relationships with obesity-related markers, insulin sensitivity and pancreatic β cell function. Method: We studied the levels of serum SPX in 40 obese and 32 normal weight pre-puberty children (mean age was 8.59 ± 1.82 and 8.15 ± 2.03 years in obesity and control groups respectively). We investigated the levels of body mass index, blood pressure, lipids, glucose, insulin, Homeostasis model assessment for insulin-resistant (HOMA-IR, HOMA for β-cell function [HOMA-β]), insulinogenic index and C-peptide index and analyzed their correlations with SPX levels. Results: SPX levels were significantly decreased in obese children compared to controls. Moreover, serum SPX levels were lower in IR obese subjects in contrast with the non-IR obese subjects. Serum SPX concentrations correlated negatively and significantly with triglycerides, systolic blood pressure, diastolic blood pressure, fasting insulin level, HOMA-IR, insulinogenic index, and HOMA-β levels in obese children. Conclusions: In summary, serum SPX levels significantly decreased in obese children and negatively correlated with insulin resistance and pancreatic β cell function indicators. Therefore, SPX may play a protective role in the process of glucose homeostasis and is closely related to β cell function in obese children.

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