scholarly journals Glucose homeostasis, insulin secretion, and islet phospholipids in mice that overexpress iPLA2β in pancreatic β-cells and in iPLA2β-null mice

2008 ◽  
Vol 294 (2) ◽  
pp. E217-E229 ◽  
Author(s):  
Shunzhong Bao ◽  
David A. Jacobson ◽  
Mary Wohltmann ◽  
Alan Bohrer ◽  
Wu Jin ◽  
...  

Studies with genetically modified insulinoma cells suggest that group VIA phospholipase A2 (iPLA2β) participates in amplifying glucose-induced insulin secretion. INS-1 insulinoma cells that overexpress iPLA2β, for example, exhibit amplified insulin-secretory responses to glucose and cAMP-elevating agents. To determine whether similar effects occur in whole animals, we prepared transgenic (TG) mice in which the rat insulin 1 promoter (RIP) drives iPLA2β overexpression, and two characterized TG mouse lines exhibit similar phenotypes. Their pancreatic islet iPLA2β expression is increased severalfold, as reflected by quantitative PCR of iPLA2β mRNA, immunoblotting of iPLA2β protein, and iPLA2β enzymatic activity. Immunofluorescence microscopic studies of pancreatic sections confirm iPLA2β overexpression in RIP-iPLA2β-TG islet β-cells without obviously perturbed islet morphology. Male RIP-iPLA2β-TG mice exhibit lower blood glucose and higher plasma insulin concentrations than wild-type (WT) mice when fasting and develop lower blood glucose levels in glucose tolerance tests, but WT and TG blood glucose levels do not differ in insulin tolerance tests. Islets from male RIP-iPLA2β-TG mice exhibit greater amplification of glucose-induced insulin secretion by a cAMP-elevating agent than WT islets. In contrast, islets from male iPLA2β-null mice exhibit blunted insulin secretion, and those mice have impaired glucose tolerance. Arachidonate incorporation into and the phospholipid composition of RIP-iPLA2β-TG islets are normal, but they exhibit reduced Kv2.1 delayed rectifier current and prolonged glucose-induced action potentials and elevations of cytosolic Ca2+ concentration that suggest a molecular mechanism for the physiological role of iPLA2β to amplify insulin secretion.

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2330 ◽  
Author(s):  
Ari ◽  
Murdun ◽  
Koutnik ◽  
Goldhagen ◽  
Rogers ◽  
...  

Diseases involving inflammation and oxidative stress can be exacerbated by high blood glucose levels. Due to tight metabolic regulation, safely reducing blood glucose can prove difficult. The ketogenic diet (KD) reduces absolute glucose and insulin, while increasing fatty acid oxidation, ketogenesis, and circulating levels of β-hydroxybutyrate (βHB), acetoacetate (AcAc), and acetone. Compliance to KD can be difficult, so alternative therapies that help reduce glucose levels are needed. Exogenous ketones provide an alternative method to elevate blood ketone levels without strict dietary requirements. In this study, we tested the changes in blood glucose and ketone (βHB) levels in response to acute, sub-chronic, and chronic administration of various ketogenic compounds in either a post-exercise or rested state. WAG/Rij (WR) rats, a rodent model of human absence epilepsy, GLUT1 deficiency syndrome mice (GLUT1D), and wild type Sprague Dawley rats (SPD) were assessed. Non-pathological animals were also assessed across different age ranges. Experimental groups included KD, standard diet (SD) supplemented with water (Control, C) or with exogenous ketones: 1, 3-butanediol (BD), βHB mineral salt (KS), KS with medium chain triglyceride/MCT (KSMCT), BD acetoacetate diester (KE), KE with MCT (KEMCT), and KE with KS (KEKS). In rested WR rats, the KE, KS, KSMCT groups had lower blood glucose level after 1 h of treatment, and in KE and KSMCT groups after 24 h. After exercise, the KE, KSMCT, KEKS, and KEMCT groups had lowered glucose levels after 1 h, and in the KEKS and KEMCT groups after 7 days, compared to control. In GLUT1D mice without exercise, only KE resulted in significantly lower glucose levels at week 2 and week 6 during a 10 weeks long chronic feeding study. In 4-month and 1-year-old SPD rats in the post-exercise trials, blood glucose was significantly lower in KD and KE, and in KEMCT groups, respectively. After seven days, the KSMCT group had the most significantly reduced blood glucose levels, compared to control. These results indicate that exogenous ketones were efficacious in reducing blood glucose levels within and outside the context of exercise in various rodent models of different ages, with and without pathology.


2017 ◽  
Vol 235 (3) ◽  
pp. 237-249 ◽  
Author(s):  
Chao Li ◽  
Bin Yang ◽  
Zhihao Xu ◽  
Eric Boivin ◽  
Mazzen Black ◽  
...  

Oxidative stress is a major cause of islet injury and dysfunction during isolation and transplantation procedures. Cyanidin-3-O-glucoside (C3G), which is present in various fruits and vegetables especially in Chinese bayberry, shows a potent antioxidant property. In this study, we determined whether C3G could protect neonatal porcine islets (NPI) from reactive oxygen species (H2O2)-induced injury in vitro and promote the function of NPI in diabetic mice. We found that C3G had no deleterious effect on NPI and that C3G protected NPI from damage induced by H2O2. Significantly higher hemeoxygenase-1 (HO1) gene expression was detected in C3G-treated NPI compared to untreated islets before and after transplantation (P < 0.05). Western blot analysis showed a significant increase in the levels of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphatidylinositol 3-kinase (PI3K/Akt) proteins in C3G-treated NPI compared to untreated islets. C3G induced the nuclear translocation of nuclear erythroid 2-related factor 2 (NRF2) and the significant elevation of HO1 protein. Recipients of C3G-treated NPI with or without C3G-supplemented drinking water achieved normoglycemia earlier compared to recipients of untreated islets. Mice that received C3G-treated islets with or without C3G-supplemented water displayed significantly lower blood glucose levels at 5–10 weeks post-transplantation compared to mice that received untreated islets. Mice that received C3G-treated NPI and C3G-supplemented drinking water had significantly (P < 0.05) lower blood glucose levels at 7 and 8 weeks post-transplantation compared to mice that received C3G-treated islets. These findings suggest that C3G has a beneficial effect on NPI through the activation of ERK1/2- and PI3K/AKT-induced NRF2-mediated HO1 signaling pathway.


Author(s):  
Okka Scholz ◽  
Silke Otter ◽  
Alena Welters ◽  
Laura Wörmeyer ◽  
Jurij Dolenšek ◽  
...  

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Jay M. Pescatore ◽  
Juan Sarmiento ◽  
Ruben A. Hernandez-Acosta ◽  
Britt Skaathun ◽  
Nancy Quesada-Rodriguez ◽  
...  

Abstract Context Corticosteroids, specifically dexamethasone, have become the mainstay of treatment for moderate to severe COVID-19. Although the RECOVERY trial did not report adverse effects of corticosteroids, the METCOVID (Methylprednisolone as Adjunctive Therapy for Patients Hospitalized with COVID-19) study reported a higher blood glucose level in patients receiving methylprednisolone. Objectives This study aims to analyze the association between corticosteroids and COVID-19–related outcomes in patients admitted to the medical ICU (MICU) for COVID-19 pneumonia. Methods This is an observational study of 141 patients admitted to the MICU between March 18 and June 7, 2020. Data on demographics, laboratory and imaging studies, and clinical course were obtained, including data on corticosteroid use. Bivariate analyses and logistic regression were performed between patient characteristics and mortality and successful extubation. Results Of the 141 patients, 86 required mechanical ventilation, 50 received steroids, and 71 died. Regarding demographics, patients had a median age of 58 (interquartile range [IQR] 48, 65), Hispanic (57.4%, n=81), and non-Hispanic Black (37.5%, n=53). The most prevalent comorbidities were hypertension (49.6%, n=70) and diabetes (48.2%, n=68). Lower blood glucose levels on admission (125.5 vs. 148 mg/dL, p=0.025) and lower peak blood glucose levels on corticosteroids (215.5 vs. 361 mg/dL, p=0.0021) were associated with lower prevalence of mortality. Patients who were successfully extubated had a lower admission blood glucose (126.5 vs. 149 mg/dL, p=0.0074) and lower peak blood glucose on corticosteroids (217 vs. 361 mg/dL, p=0.0023). Conclusions Lower blood glucose on admission and lower maximum blood glucose on corticosteroids were associated with lower odds of mortality and successful extubation, regardless of preexisting diabetes. Hyperglycemia may be negating any potential benefit of corticosteroid therapy. These findings suggest that glucose control could be a parameter that impacts the outcome of patients receiving corticosteroids for COVID-19 pneumonia.


MEDULA ◽  
2019 ◽  
Vol 6 (3) ◽  
Author(s):  
Parawansah Parawansah

ABSTRACTBackground: Green  gedi leaves  (Abelmoschus manihot (L.)  Medik)  is one plant that has efficacy in treating various diseases one of which is antidiabetic. The nature of the active substance green gedi leaves that capable lower blood glucose levels are flavonoids. Purpose: The purpose of this  study  was  to  determine  the effective  concentration  of  the  extract  of  green  gedi  leaves (Abelmoschus  manihot  (L.)  Medik)  to  lower  the  blood  glucose  levels on  mice  Induced  by Streptozotocin. Method: This type of research is experimental research that consists of 5 treatments with 3 variations dose and 2 controls. The study was conducted by measuring the blo od glucose levels in mice, blood glucose levels after induction to return normal blood glucose levels after oral administration with a suspension of Na. CMC as a control, and the suspension glibenclamid as a comparison with the extract of green gedi leaves concentration of 30 mg/KgBB, 60 mg/KgBB and 90 mg/KgBB with a time of observation for seven days. Result: The data obtained were analyzed using ANOVA and LSD. Conclusion: From this study that the green gedi leaf extract (Abelmoschus manihot (L.) Medik) at a concentration of 90 mg/kgBB is more effectife to give antidiabetic effect with the average reduction in blood glucose levels reach 68,67 mg/dL to mice.Keywords: antidiabetic, abelmoschus manihot (L.) Medik, green gedi leaves, Streptozotocin


2017 ◽  
Vol 114 (25) ◽  
pp. 6611-6616 ◽  
Author(s):  
May-yun Wang ◽  
Xinxin Yu ◽  
Young Lee ◽  
Sara Kay McCorkle ◽  
Shiuhwei Chen ◽  
...  

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of antidiabetic drug used for the treatment of diabetes. These drugs are thought to lower blood glucose by blocking reabsorption of glucose by SGLT2 in the proximal convoluted tubules of the kidney. To investigate the effect of inhibiting SGLT2 on pancreatic hormones, we treated perfused pancreata from rats with chemically induced diabetes with dapagliflozin and measured the response of glucagon secretion by alpha cells in response to elevated glucose. In these type 1 diabetic rats, glucose stimulated glucagon secretion by alpha cells; this was prevented by dapagliflozin. Two models of type 2 diabetes, severely diabetic Zucker rats and db/db mice fed dapagliflozin, showed significant improvement of blood glucose levels and glucose disposal, with reduced evidence of glucagon signaling in the liver, as exemplified by reduced phosphorylation of hepatic cAMP-responsive element binding protein, reduced expression of phosphoenolpyruvate carboxykinase 2, increased hepatic glycogen, and reduced hepatic glucose production. Plasma glucagon levels did not change significantly. However, dapagliflozin treatment reduced the expression of the liver glucagon receptor. Dapagliflozin in rodents appears to lower blood glucose levels in part by suppressing hepatic glucagon signaling through down-regulation of the hepatic glucagon receptor.


2020 ◽  
Vol 11 ◽  
pp. 204201882096506
Author(s):  
Basma Haris ◽  
Saras Saraswathi ◽  
Khalid Hussain

Hyperinsulinaemic hypoglycaemia (HH) is a biochemical finding of low blood glucose levels due to the dysregulation of insulin secretion from pancreatic β-cells. Under normal physiological conditions, glucose metabolism is coupled to β-cell insulin secretion so that blood glucose levels are maintained within the physiological range of 3.5–5.5 mmol/L. However, in HH this coupling of glucose metabolism to insulin secretion is perturbed so that insulin secretion becomes unregulated. HH typically occurs in the neonatal, infancy and childhood periods and can be due to many different causes. Adults can also present with HH but the causes in adults tend to be different. Somatostatin (SST) is a peptide hormone that is released by the delta cells (δ-cells) in the pancreas. It binds to G protein-coupled SST receptors to regulate a variety of location-specific and selective functions such as hormone inhibition, neurotransmission and cell proliferation. SST plays a potent role in the regulation of both insulin and glucagon secretion in response to changes in glucose levels by negative feedback mechanism. The half-life of SST is only 1–3 min due to quick degradation by peptidases in plasma and tissues. Thus, a direct continuous intravenous or subcutaneous infusion is required to achieve the therapeutic effect. These limitations prompted the discovery of SST analogues such as octreotide and lanreotide, which have longer half-lives and therefore can be administered as injections. SST analogues are used to treat different forms of HH in children and adults and therapeutic effect is achieved by suppressing insulin secretion from pancreatic β-cells by complex mechanisms. These treatments are associated with several side effects, especially in the newborn period, with necrotizing enterocolitis being the most serious side effect and hence SS analogues should be used with extreme caution in this age group.


2019 ◽  
Vol 1 (1) ◽  
pp. 72-80
Author(s):  
Hesti Riany

Diabetes mellitus (DM) is a chronic metabolic disease. It was caused by lack of insulin or cells cannot use insulin so that blood glucose becomes high (hyperglycemia). And it will cause other systemic diseases of the disease (metabolic syndrome) that can increase the factor of death. Coffee is one of the consumed plants that contain antioxidants and chlorogenic acid that have a role as antihyperglycemia. In other hand Jambi as one of the coffee producing regions (arabica, robust and liberica) in Sumatra and it has a potency as a coffee producer. In addition, people's habits in consuming coffee have the opportunity to be one solution in overcoming diabetes. This study aimed to determine the effect of hyperglycemia disease. The method was experimental with 5 treatments (metformin, arabica, robust, liberica and aquades) and 3 replications. Before threatments mice were injected with streptozotosin in order to be hyperglycemia, then mice with blood glucose ≥ 116 mg / dl were measured their blood glucose, weight and made the histology of the liver. Then the datas were analyzed using ANAVA. The results showed that Jambi coffee (arabica, robust and liberica) can lower blood glucose levels hyperglycemia mice until day 16. And the treatment with liberica coffee lowers hyperglycemia with the lowest glucose levels. While the histological features of mice liver showed lower cell degeneration especially in mice by coffee treatment, especially arabica coffee.


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