scholarly journals Lipocalin-2 counteracts metabolic dysregulation in obesity and diabetes

2020 ◽  
Vol 217 (10) ◽  
Author(s):  
Ioanna Mosialou ◽  
Steven Shikhel ◽  
Na Luo ◽  
Peristera Ioanna Petropoulou ◽  
Konstantinos Panitsas ◽  
...  
Keyword(s):  
Food Intake ◽  
Glucose Metabolism ◽  
Cell Function ◽  
Endocrine Function ◽  
Protective Mechanism ◽  
Lipocalin 2 ◽  
Obese Mice ◽  
Β Cell ◽  
Obesity And Diabetes ◽  
Β Cell Function

Regulation of food intake is a recently identified endocrine function of bone that is mediated by Lipocalin-2 (LCN2). Osteoblast-secreted LCN2 suppresses appetite and decreases fat mass while improving glucose metabolism. We now show that serum LCN2 levels correlate with insulin levels and β-cell function, indices of healthy glucose metabolism, in obese mice and obese, prediabetic women. However, LCN2 serum levels also correlate with body mass index and insulin resistance in the same individuals and are increased in obese mice. To dissect this apparent discrepancy, we modulated LCN2 levels in mice. Silencing Lcn2 expression worsens metabolic dysfunction in genetic and diet-induced obese mice. Conversely, increasing circulating LCN2 levels improves metabolic parameters and promotes β-cell function in mouse models of β-cell failure acting as a growth factor necessary for β-cell adaptation to higher metabolic load. These results indicate that LCN2 up-regulation is a protective mechanism to counteract obesity-induced glucose intolerance by decreasing food intake and promoting adaptive β-cell proliferation.

scholarly journals Effect of a mitochondrial-targeted coenzyme Q analog on pancreatic β-cell function and energetics in high fat fed obese mice

2018 ◽  
Vol 6 (3) ◽  
pp. e00393 ◽  
Author(s):  
Yumi Imai ◽  
Brian D. Fink ◽  
Joseph A. Promes ◽  
Chaitanya A. Kulkarni ◽  
Robert J. Kerns ◽  
...  
Keyword(s):  
Cell Function ◽  
Coenzyme Q ◽  
Pancreatic Β Cell ◽  
Obese Mice ◽  
High Fat ◽  
Β Cell ◽  
Β Cell Function

scholarly journals Sustained maternal inflammation during the early third-trimester yields intrauterine growth restriction, impaired skeletal muscle glucose metabolism, and diminished β-cell function in fetal sheep1,2

2019 ◽  
Vol 97 (12) ◽  
pp. 4822-4833 ◽  
Author(s):  
Caitlin N Cadaret ◽  
Elena M Merrick ◽  
Taylor L Barnes ◽  
Kristin A Beede ◽  
Robert J Posont ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Intrauterine Growth Restriction ◽  
Cell Function ◽  
Ex Vivo ◽  
White Blood Cells ◽  
Β Cell ◽  
Intrauterine Growth ◽  
Maternal Inflammation ◽  
Β Cell Function

Abstract Maternal inflammation causes fetal intrauterine growth restriction (IUGR), but its impact on fetal metabolism is not known. Thus, our objective was to determine the impact of sustained maternal inflammation in late gestation on fetal inflammation, skeletal muscle glucose metabolism, and insulin secretion. Pregnant ewes were injected every third day from the 100th to 112th day of gestation (term = 150 d) with saline (controls) or lipopolysaccharide (LPS) to induce maternal inflammation and IUGR (MI-IUGR). Fetal femoral blood vessels were catheterized on day 118 to assess β-cell function on day 123, hindlimb glucose metabolic rates on day 124, and daily blood parameters from days 120 to 125. Fetal muscle was isolated on day 125 to assess ex vivo glucose metabolism. Injection of LPS increased (P < 0.05) rectal temperatures, circulating white blood cells, and plasma tumor necrosis factor α (TNFα) concentrations in MI-IUGR ewes. Maternal leukocytes remained elevated (P < 0.05) and TNFα tended to remain elevated (P < 0.10) compared with controls almost 2 wk after the final LPS injection. Total white blood cells, monocytes, granulocytes, and TNFα were also greater (P < 0.05) in MI-IUGR fetuses than controls over this period. MI-IUGR fetuses had reduced (P < 0.05) blood O2 partial pressures and greater (P < 0.05) maternofetal O2 gradients, but blood glucose and maternofetal glucose gradients did not differ from controls. Basal and glucose-stimulated insulin secretion were reduced (P < 0.05) by 32% and 42%, respectively, in MI-IUGR fetuses. In vivo hindlimb glucose oxidation did not differ between groups under resting conditions but was 47% less (P < 0.05) in MI-IUGR fetuses than controls during hyperinsulinemia. Hindlimb glucose utilization did not differ between fetal groups. At day 125, MI-IUGR fetuses were 22% lighter (P < 0.05) than controls and tended to have greater (P < 0.10) brain/BW ratios. Ex vivo skeletal muscle glucose oxidation did not differ between groups in basal media but was less (P < 0.05) for MI-IUGR fetuses in insulin-spiked media. Glucose uptake rates and phosphorylated-to-total Akt ratios were less (P < 0.05) in muscle from MI-IUGR fetuses than controls regardless of media. We conclude that maternal inflammation leads to fetal inflammation, reduced β-cell function, and impaired skeletal muscle glucose metabolism that persists after maternal inflammation ceases. Moreover, fetal inflammation may represent a target for improving metabolic dysfunction in IUGR fetuses.

scholarly journals Maternal high-fat diet impairs glucose metabolism, β-cell function and proliferation in the second generation of offspring rats

2017 ◽  
Vol 14 (1) ◽  
Author(s):  
Yan-Hong Huang ◽  
Ting-Ting Ye ◽  
Chong-Xiao Liu ◽  
Lei Wang ◽  
Yuan-Wen Chen ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
High Fat Diet ◽  
Second Generation ◽  
Cell Function ◽  
High Fat ◽  
Β Cell ◽  
Β Cell Function

scholarly journals Continuous Deterioration of Glucose Metabolism in Treatment-Naive Male Patients with Human Immunodeficiency Virus and Treated with Tenofovir Plus Lamivudine Plus Efavirenz for 156 Weeks

2021 ◽  
Author(s):  
Dafeng Liu ◽  
Xinyi Zhang ◽  
Ruifeng Zhou ◽  
Lin Cai ◽  
Dongmei Yan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Human Immunodeficiency Virus ◽  
Glucose Metabolism ◽  
Cell Count ◽  
Cell Function ◽  
Β Cell ◽  
Immunodeficiency Virus ◽  
Treatment Naïve ◽  
Β Cell Function ◽  
Cd8 Cell

Abstract Introduction: The dynamic characteristics of glucose metabolism and its risk factors in people living with human immunodeficiency virus (PLWH) accepted primary treatment with the efavirenz (EFV) plus lamivudine (3TC) plus tenofovir (TDF) (EFV+3TC+TDF) regimen are unclear and warrant investigation.Methods: This study was designed using follow-up study. Sixty-one male treatment-naive PLWH were treated with EFV+3TC+TDF regimen for 156 weeks. The glucose metabolism dynamic characteristics, the main risk factors and the differences among the three CD4+ count groups were analyzed.Result: In treatment-naive male PLWH who accepted treatment with the EFV+3TC+TDF regimen for 156 weeks, a continuous increase in the fasting plasma glucose (FPG) level, the rate of impaired fasting glucose (IFG) and the glycosylated hemoglobin (HbA1c) level were found. These changes were not due to insulin resistance but rather to significantly reduced islet β cell function, according to the homeostasis model assessment of β cell function (HOMA-β). Moreover, the lower the baseline CD4+ T cell count was, the higher the FPG level and the lower the HOMA-β value. Furthermore the main risk factors for the FPG levels were the CD3+CD8+ cell count and viral load (VL), and the factors contributing to the HOMA-β values were the alanine aminotransferase (ALT) level, VL and CD3+CD8+ cell count.Conclusions: These findings provide guidance to clinicians who are monitoring FPG levels closely and are concerned about IFG and decreased islet β cell function during ART with the EFV+3TC+TDF regimen for long-term application.

scholarly journals Glucose and Insulin Stimulate Heparin-releasable Lipoprotein Lipase Activity in Mouse Islets and INS-1 Cells

2001 ◽  
Vol 276 (15) ◽  
pp. 12162-12168 ◽  
Author(s):  
Wilhelm S. Cruz ◽  
Guim Kwon ◽  
Connie A. Marshall ◽  
Michael L. McDaniel ◽  
Clay F. Semenkovich
Keyword(s):  
Fatty Acids ◽  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Lipoprotein Lipase ◽  
Cell Function ◽  
Β Cells ◽  
Β Cell ◽  
Protein Mass ◽  
Β Cell Function

Lipoprotein lipase (LpL) provides tissues with triglyceride-derived fatty acids. Fatty acids affect β-cell function, and LpL overexpression decreases insulin secretion in cell lines, but whether LpL is regulated in β-cells is unknown. To test the hypothesis that glucose and insulin regulate LpL activity in β-cells, we studied pancreatic islets and INS-1 cells. Acute exposure of β-cells to physiological concentrations of glucose stimulated both total cellular LpL activity and heparin-releasable LpL activity. Glucose had no effect on total LpL protein mass but instead promoted the appearance of LpL protein in a heparin-releasable fraction, suggesting that glucose stimulates the translocation of LpL from intracellular to extracellular sites in β-cells. The induction of heparin-releasable LpL activity was unaffected by treatment with diazoxide, an inhibitor of insulin exocytosis that does not alter glucose metabolism but was blocked by conditions that inhibit glucose metabolism.In vitrohyperinsulinemia had no effect on LpL activity in the presence of low concentrations of glucose but increased LpL activity in the presence of 20 mmglucose. Using dual-laser confocal microscopy, we detected intracellular LpL in vesicles distinct from those containing insulin. LpL was also detected at the cell surface and was displaced from this site by heparin in dispersed islets and INS-1 cells. These results show that glucose metabolism controls the trafficking of LpL activity in β-cells independent of insulin secretion. They suggest that hyperglycemia and hyperinsulinemia associated with insulin resistance may contribute to progressive β-cell dysfunction by increasing LpL-mediated delivery of lipid to islets.

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