Carine Marmentini

Universidade Estadual de Campinas (UNICAMP)

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Antônio C. Boschero

Universidade Estadual de Campinas (UNICAMP)

Gabriela Moreira Soares

Universidade Estadual de Campinas (UNICAMP)

Mirian Ayumi Kurauti

Universidade Estadual de Maringá

Gabriela Alves Bronczek

Universidade Estadual de Campinas (UNICAMP)

Sandra Lucinei Balbo

Universidade Estadual do Oeste do Paraná

José Maria Costa-Júnior

Universidade Estadual de Campinas (UNICAMP)

Everardo M. Carneiro

Universidade Estadual de Campinas (UNICAMP)

Lucas Zangerolamo

Universidade Estadual de Campinas (UNICAMP)

Cecília Edna Mareze-Costa

Universidade Estadual de Maringá

Jean Franciesco Vettorazzi

Universidade Federal da Integração Latino-Americana

Cooperative Institutions

Universidade Estadual de Campinas (UNICAMP)

Universidade Estadual de Maringá

Universidade Estadual do Oeste do Paraná

Universidade Estadual de Londrina

Universidade de São Paulo

Hospital de Clínicas da Unicamp

Universidade de Ribeirão Preto

Universidade Estadual Paulista (Unesp)

Diabetes Australia

European Union of Medical Specialists

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Resistance exercise training improves glucose homeostasis by enhancing insulin secretion in C57BL/6 mice

Scientific Reports (2021)

Gabriela Alves Bronczek Gabriela Moreira Soares Jaqueline Fernandes de Barros Jean Franciesco Vettorazzi Mirian Ayumi Kurauti

Abstract Resistance exercise exerts beneficial effects on glycemic control, which could be mediated by exercise-induced humoral factors released in the bloodstream. Here, we used C57Bl/6 healthy mice, submitted to resistance exercise training for 10 weeks. Trained mice presented higher muscle weight and maximum voluntary carrying capacity, combined with reduced body weight gain and fat deposition. Resistance training improved glucose tolerance and reduced glycemia, with no alterations in insulin sensitivity. In addition, trained mice displayed higher insulinemia in fed state, associated with increased glucose-stimulated insulin secretion. Islets from trained mice showed reduced expression of genes related to endoplasmic reticulum (ER) stress, associated with increased expression of Ins2. INS-1E beta-cells incubated with serum from trained mice displayed similar pattern of insulin secretion and gene expression than isolated islets from trained mice. When exposed to CPA (an ER stress inducer), the serum from trained mice partially preserved the secretory function of INS-1E cells, and prevented CPA-induced apoptosis. These data suggest that resistance training, in healthy mice, improves glucose homeostasis by enhancing insulin secretion, which could be driven, at least in part, by humoral factors.

Homeostasis

10.1038/s41598-021-88105-x

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Citations (17)

Rosiglitazone protects INS-1E cells from human islet amyloid polypeptide toxicity

European Journal of Pharmacology (2022)

Carine Marmentini Dimitrius Santiago P.S.F. Guimarães Tanes Lima Francisco Breno Silva Teófilo Natália S. da Silva

Rosiglitazone

Amyloid (mycology)

Amylin

Pancreatic Islets

10.1016/j.ejphar.2022.175122

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Citations (6)

The bile acid TUDCA reduces age-related hyperinsulinemia in mice

Scientific Reports (2022)

Lucas Zangerolamo Marina Carvalho Letícia Barssotti Gabriela Moreira Soares Carine Marmentini

Abstract Aging is associated with glucose metabolism disturbances, such as insulin resistance and hyperinsulinemia, which contribute to the increased prevalence of type 2 diabetes (T2D) and its complications in the elderly population. In this sense, some bile acids have emerged as new therapeutic targets to treat TD2, as well as associated metabolic disorders. The taurine conjugated bile acid, tauroursodeoxycholic acid (TUDCA) improves glucose homeostasis in T2D, obesity, and Alzheimer's disease mice model. However, its effects in aged mice have not been explored yet. Here, we evaluated the actions of TUDCA upon glucose-insulin homeostasis in aged C57BL/6 male mice (18-month-old) treated with 300 mg/kg of TUDCA or its vehicle. TUDCA attenuated hyperinsulinemia and improved glucose homeostasis in aged mice, by enhancing liver insulin-degrading enzyme (IDE) expression and insulin clearance. Furthermore, the improvement in glucose-insulin homeostasis in these mice was accompanied by a reduction in adiposity, associated with adipocyte hypertrophy, and lipids accumulation in the liver. TUDCA-treated aged mice also displayed increased energy expenditure and metabolic flexibility, as well as a better cognitive ability. Taken together, our data highlight TUDCA as an interesting target for the attenuation of age-related hyperinsulinemia and its deleterious effects on metabolism.

Hyperinsulinemia

Tauroursodeoxycholic acid

Homeostasis

10.1038/s41598-022-26915-3

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Citations (8)

Insulin in combination with pioglitazone prevents advanced cachexia in 256-Walker tumor-bearing rats: effect is greater than treatment alone and is associated with improved insulin sensitivity

Pharmacological Reports (2023)

Daniele Romani Miksza Giuliana Regina Biazi Isabele Gonçalves Frasson Winny Beatriz de Souza Galia Laura Socio Ferraz

Pioglitazone

10.1007/s43440-023-00533-w

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Aging Reduces Insulin Clearance in Mice

Frontiers in Endocrinology (2021)

Carine Marmentini Gabriela Moreira Soares Gabriela Alves Bronczek Silvano Piovan Cecília Edna Mareze-Costa

Hyperinsulinemia is frequently associated with aging and may cause insulin resistance in elderly. Since insulin secretion and clearance decline with age, hyperinsulinemia seems to be maintained, primarily, due to a decrease in the insulin clearance. To investigate these aging effects, 3- and 18-month-old male C57BL/6 mice were subjected to intraperitoneal glucose and insulin tolerance tests (ipGTT and ipITT) and, during the ipGTT, plasma c-peptide and insulin were measure to evaluate in vivo insulin clearance. Glucose-stimulated insulin secretion in isolated pancreatic islets was also assessed, and liver samples were collected for molecular analyses (western blot). Although insulin sensitivity was not altered in the old mice, glucose tolerance, paradoxically, seems to be increased, accompanied by higher plasma insulin, during ipGTT. While insulin secretion did not increase, insulin clearance was reduced in the old mice, as suggested by the lower c-peptide:insulin ratio, observed during ipGTT. Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) and insulin-degrading enzyme (IDE), as well as the activity of this enzyme, were reduced in the liver of old mice, justifying the decreased insulin clearance observed in these mice. Therefore, loss of hepatic CEACAM1 and IDE function may be directly related to the decline in insulin clearance during aging.

Hyperinsulinemia

Insulin oscillation

Glucose tolerance test

10.3389/fendo.2021.679492

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Citations (32)

Resistance Training Improves Beta Cell Glucose Sensing and Survival in Diabetic Models

International Journal of Molecular Sciences (2022)

Gabriela Alves Bronczek Gabriela Moreira Soares Carine Marmentini Antônio C. Boschero José Maria Costa-Júnior

Resistance training increases insulin secretion and beta cell function in healthy mice. Here, we explored the effects of resistance training on beta cell glucose sensing and survival by using in vitro and in vivo diabetic models. A pancreatic beta cell line (INS-1E), incubated with serum from trained mice, displayed increased insulin secretion, which could be linked with increased expression of glucose transporter 2 (GLUT2) and glucokinase (GCK). When cells were exposed to pro-inflammatory cytokines (in vitro type 1 diabetes), trained serum preserved both insulin secretion and GCK expression, reduced expression of proteins related to apoptotic pathways, and also protected cells from cytokine-induced apoptosis. Using 8-week-old C57BL/6 mice, turned diabetic by multiple low doses of streptozotocin, we observed that resistance training increased muscle mass and fat deposition, reduced fasting and fed glycemia, and improved glucose tolerance. These findings may be explained by the increased fasting and fed insulinemia, along with increased beta cell mass and beta cell number per islet, observed in diabetic-trained mice compared to diabetic sedentary mice. In conclusion, we believe that resistance training stimulates the release of humoral factors which can turn beta cells more resistant to harmful conditions and improve their response to a glucose stimulus.

GLUT2

Glucokinase

Carbohydrate Metabolism

10.3390/ijms23169427

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Citations (2)

Vertical sleeve gastrectomy improves glucose-insulin homeostasis by enhancing β-cell function and survival via FGF15/19

AJP Endocrinology and Metabolism (2023)

Gabriela Moreira Soares Sandra Lucinei Balbo Gabriela Alves Bronczek Jean Franciesco Vettorazzi Carine Marmentini

Vertical sleeve gastrectomy (VSG) decreases insulin secretion, endoplasmic reticulum (ER) stress, and inflammation in pancreatic islets from obese mice. In addition, VSG increased fibroblast growth factor (FGF)15 circulating levels in obese mice, as well as the expression of FGF receptor 1 ( Fgfr1) and its coreceptor β-klotho ( Klb), both in pancreatic islets from VSG mice and in INS-1E β-cells treated with the serum from these mice. Serum from operated mice protects INS-1E cells from dysfunction and apoptosis, which was mediated by FGF15/19.

Pancreatic Islets

Homeostasis

10.1152/ajpendo.00218.2023

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Citations (2)

Sleeve Gastrectomy-Induced Weight Loss Increases Insulin Clearance in Obese Mice

International Journal of Molecular Sciences (2023)

Gabriela Moreira Soares Luana Emanuelly Sinhori Lopes Sandra Lucinei Balbo Carine Marmentini Gabriela Alves Bronczek

Sleeve gastrectomy (SG) successfully recovers metabolic homeostasis in obese humans and rodents while also resulting in the normalization of insulin sensitivity and insulinemia. Reduced insulin levels have been attributed to lower insulin secretion and increased insulin clearance in individuals submitted to SG. Insulin degradation mainly occurs in the liver in a process controlled, at least in part, by the insulin-degrading enzyme (IDE). However, research has yet to explore whether liver IDE expression or activity is altered after SG surgery. In this study, C57BL/6 mice were fed a chow (CTL) or high-fat diet (HFD) for 10 weeks. Afterward, the HFD mice were randomly assigned to two groups: sham-surgical (HFD-SHAM) and SG-surgical (HFD-SG). Here, we confirmed that SG improves glucose-insulin homeostasis in obese mice. Additionally, SG reduced insulinemia by reducing insulin secretion, assessed by the analysis of plasmatic C-peptide content, and increasing insulin clearance, which was evaluated through the calculation of the plasmatic C-peptide:insulin ratio. Although no changes in hepatic IDE activity were observed, IDE expression was higher in the liver of HFD-SG compared with HFD-SHAM mice. These results indicate that SG may be helpful to counteract obesity-induced hyperinsulinemia by increasing insulin clearance, likely through enhanced liver IDE expression.

Sleeve gastrectomy

10.3390/ijms24021729

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Citations (1)

Glyphosate-based herbicide exposure during pregnancy and lactation malprograms the male reproductive morphofunction in F1 offspring

Journal of Developmental Origins of Health and Disease (2019)

Jakeline Liara Teleken Ellen Carolina Zawoski Gomes Carine Marmentini Milara Bruna Moi Rosane Aparecida Ribeiro

Abstract One of the most consumed pesticides in the world is glyphosate, the active ingredient in the herbicide ROUNDUP®. Studies demonstrate that glyphosate can act as an endocrine disruptor and that exposure to this substance at critical periods in the developmental period may program the fetus to induce reproductive damage in adulthood. Our hypothesis is that maternal exposure to glyphosate during pregnancy and lactation in mice will affect the development of male reproductive organs, impairing male fertility during adult life. Female mice consumed 0.5% glyphosate-ROUNDUP® in their drinking water [glyphosate-based herbicide (GBH) group] or filtered water [control (CTRL) group] from the fourth day of pregnancy until the end of the lactation period. Male F1 offspring were designated, according to their mother’s treatment, as CTRL-F1 and GBH-F1. Female mice that drank glyphosate displayed reduced body weight (BW) gain during gestation, but no alterations in litter size. Although GBH male F1 offspring did not exhibit modifications in BW, they demonstrated delayed testicular descent. Furthermore, at PND150, GBH-F1 mice presented a lower number of spermatozoa in the cauda epididymis and reduced epithelial height of the seminiferous epithelium. Notably, intratesticular testosterone concentrations were enhanced in GBH-F1 mice; we show that it is an effect associated with increased plasma and pituitary concentrations of luteinizing hormone. Therefore, data indicate that maternal exposure to glyphosate-ROUNDUP® during pregnancy and lactation may lead to decreased spermatogenesis and disruptions in hypothalamus–pituitary–testicular axis regulation in F1 offspring.

Litter

Endocrine disruptor

10.1017/s2040174419000382

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Citations (38)

Insulin and aging

Vitamins and hormones (2021)

Mirian Ayumi Kurauti Gabriela Moreira Soares Carine Marmentini Gabriela Alves Bronczek Renato Chaves Souto Branco

Mediator

10.1016/bs.vh.2020.12.010

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Citations (27)