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Guadalupe Navarro, Camille Allard, Jamie J Morford, Weiwei Xu, Suhuan Liu, Adrien Jr Molinas, Sierra M Butcher, Nicholas Hf Fine, Manuel Blandino-Rosano, Venkata N Sure, Sangho Yu, Rui Zhang, Heike Münzberg, David A Jacobson, Prasad V Katakam, David J Hodson, Ernesto Bernal-Mizrachi, Andrea Zsombok, Franck Mauvais-Jarvis
Androgen excess predisposes women to type 2 diabetes (T2D), but the mechanism of this is poorly understood. We report that female mice fed a Western diet and exposed to chronic androgen excess using dihydrotestosterone (DHT) exhibit hyperinsulinemia and insulin resistance associated with secondary pancreatic β cell failure, leading to hyperglycemia. These abnormalities are not observed in mice lacking the androgen receptor (AR) in β cells and partially in neurons of the mediobasal hypothalamus (MBH) as well as in mice lacking AR selectively in neurons...
June 21, 2018: JCI Insight
Petr Ježek, Martin Jabůrek, Blanka Holendová, Lydie Plecitá-Hlavatá
Fatty acid (FA)-stimulated insulin secretion (FASIS) is reviewed here in contrast to type 2 diabetes etiology, resulting from FA overload, oxidative stress, intermediate hyperinsulinemia, and inflammation, all converging into insulin resistance. Focusing on pancreatic islet β-cells, we compare the physiological FA roles with the pathological ones. Considering FAs not as mere amplifiers of glucose-stimulated insulin secretion (GSIS), but as parallel insulin granule exocytosis inductors, partly independent of the KATP channel closure, we describe the FA initiating roles in the prediabetic state that is induced by retardations in the glycerol-3-phosphate (glucose)-promoted glycerol/FA cycle and by the impaired GPR40/FFA1 (free FA1) receptor pathway, specifically in its amplification by the redox-activated mitochondrial phospholipase, iPLA2γ...
June 19, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Simon Bissonnette, Nathalie Saint-Pierre, Valerie Lamantia, Catherine Leroux, Viviane Provost, Yannick Cyr, Remi Rabasa-Lhoret, May Faraj
Background: To optimize the prevention of type 2 diabetes (T2D), high-risk obese subjects with the best metabolic recovery after a hypocaloric diet should be targeted. Apolipoprotein B lipoproteins (apoB lipoproteins) induce white adipose tissue (WAT) dysfunction, which in turn promotes postprandial hypertriglyceridemia, insulin resistance (IR), and hyperinsulinemia. Objective: The aim of this study was to explore whether high plasma apoB, or number of plasma apoB lipoproteins, identifies subjects who best ameliorate WAT dysfunction and related risk factors after a hypocaloric diet...
June 18, 2018: American Journal of Clinical Nutrition
Barbara Wlodarczyk, Anita Gasiorowska, Ewa Malecka-Panas
New-onset diabetes mellitus (DM) is one of the first symptoms of pancreatic adenocarcinoma (PDAC). The frequency of endocrine disorders is estimated between 40% and 80% in patients with pancreatic cancer. DM is a risk factor for cancer development but it may also be a consequence of the tumor growth. Data confirming the existence of a relationship between long standing type 2 DM and an increased risk of PDAC comes from numerous clinical studies. Insulin resistance phenomenon and hyperinsulinemia may result in the increased proliferation of pancreatic islets which in turn may cause a predisposition to cancer development...
June 16, 2018: Journal of Clinical Gastroenterology
Alice S Ryan, Heidi K Ortmeyer
BACKGROUND: Obesity and insulin resistance are characterized by metabolic inflexibility, a condition described as an inability to switch from fat oxidation during fasting to carbohydrate oxidation during hyperinsulinemia. The purpose of this study was to examine predictors of metabolic flexibility in 103 obese (37-59% fat), sedentary (VO2 max: 19.4 ± 0.5 ml/kg/min), postmenopausal (45-76 years) women, and changes in metabolic flexibility with exercise and weight loss interventions...
June 15, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Yadav Nisha, Zachariah Bobby, Vaibhav Wadwekar
PURPOSE: Evaluation of biochemical derangements related to metabolic syndrome in epileptic patients on treatment with Valproic acid. METHODS: This study consisted of two groups of 42 patients. Group I - Newly diagnosed patients with epileptic seizures untreated with any Anti-epileptic drugs (AEDs). Group II - Patients on treatment with Valproic acid for more than one year. Age and gender matched patients of 18-40 years were recruited. Patients who were diabetic, hypertensive, smokers, alcoholics, with persistent infection, head injuries, pregnancy and lactation were excluded from the study...
June 5, 2018: Seizure: the Journal of the British Epilepsy Association
Fred K Tabung, Weike Wang, Teresa T Fung, Stephanie A Smith-Warner, NaNa Keum, Kana Wu, Charles S Fuchs, Frank B Hu, Edward L Giovannucci
Background: Insulin response may be important in colorectal cancer development. Diet modulates insulin response and may be a modifiable factor in colorectal cancer prevention. Objective: We examined associations between hyperinsulinemic diets and colorectal cancer risk with the use of an empirical dietary index for hyperinsulinemia (EDIH), a food-based index that characterizes dietary insulinemic potential on the basis of circulating C-peptide concentrations. Design: Diet was assessed every 4 y with food-frequency questionnaires in 46,210 men (Health Professionals Follow-Up Study, 1986-2012) and 74,191 women (Nurses' Health Study, 1984-2012) to calculate EDIH scores...
June 12, 2018: American Journal of Clinical Nutrition
Christine M Burt Solorzano, Karen L Knudsen, Amy D Anderson, Eleanor G Hutchens, Jessicah S Collins, James T Patrie, John C Marshall, Christopher R McCartney
Context: Peripubertal obesity is associated with variable hyperandrogenemia, but precise mechanisms remain unclear. Objective: To assess the roles of insulin resistance, hyperinsulinemia, and luteinizing hormone (LH) in peripubertal obesity-associated hyperandrogenemia. Design: Cross-sectional analysis. Setting: Academic clinical research unit. Participants: Eleven obese (body mass index-for-age ≥ 95%) peripubertal girls...
April 20, 2018: Journal of Clinical Endocrinology and Metabolism
Zihan Yan, Zeenat A Shyr, Manuela Fortunato, Alecia Welscher, Mariana Alisio, Michael Martino, Brian N Finck, Hannah Conway, Maria S Remedi
Chronic hyperglycemia has been proposed to cause pancreatic β-cell dysfunction and loss of β-cell mass. As in human monogenic neonatal diabetes, mice expressing KATP channel gain-of-function (GOF) mutations demonstrate deficiency in insulin secretion and develop severe diabetes. As diabetes progresses, they show loss of islet insulin content and β-cell mass, secondary consequences of glucotoxicity. Co-morbidity of chronic hyperglycemia and elevated lipids, so called glucolipotoxicity, is also crucial in the pathogenesis of diabetes...
June 12, 2018: Diabetes, Obesity & Metabolism
Hung-Wen Liu, Sue-Joan Chang
The clear mechanism of moderate exercise training (Ex) in attenuating muscle loss remains elusive in diabetes. We investigated the effects of moderate exercise training on diabetes-induced nuclear factor-κB (NF-κB) activation and mitochondrial dysfunction. Skeletal muscle size and atrophy signaling pathways were examined in type 2 diabetic db/db mice with or without moderate exercise training (5.2 m/min, 1 h/day, and 5 days/week for a total of 8 weeks). Exercise training decreased serum leptin, MCP-1, and resistin levels in db/db +Ex mice, but it did not reduce symptoms of insulin resistance including hyperglycemia, hyperinsulinemia, and impaired glucose tolerance...
2018: Frontiers in Physiology
Renato Pasquali
Both prevalence and incidence of the metabolic syndrome is very high in women with polycystic ovary syndrome (PCOS). Obesity and visceral fat enlargement play a dominant role in determining the final phenotype of PCOS. Androgen excess and insulin resistance may be responsible for the development of all features of the metabolic syndrome. The major factors responsible for this association seem to be related to a triumvirate including androgen excess, insulin resistance and associated hyperinsulinemia, and obesity, particularly the abdominal-visceral phenotype...
2018: Frontiers of Hormone Research
Roghayeh Shahbazi, Makan Cheraghpour, Reza Homayounfar, Maryam Nazari, Javad Nasrollahzadeh, Sayed Hossein Davoodi
Context: It has been shown that hesperidin induces apoptosis in NALM-6 cells through inhibition of nuclear factor-kappa B (NF-κB) activation. Aims: To investigate the effect of hesperidin on inhibition of NF-κB activation through blocking phosphoinositide 3-kinase (PI3K)/Akt pathway as a main target in cancer treatment, in NALM-6 cells. Materials and Methods: NALM-6 cells were incubated with two concentrations of hesperidin (25, 50 μM) in the presence or absence of insulin (100 nM), as a potent activator of Akt...
April 2018: Journal of Cancer Research and Therapeutics
Anna L Emanuel, Nicolien C de Clercq, Annefleur M Koopen, Erik van Poelgeest, Mireille J M Serlie, Daniel H van Raalte, Mark H H Kramer, Max Nieuwdorp, Etto C Eringa, Erik H Serné
AIMS: In type 2 diabetes impaired insulin-induced muscle perfusion is thought to contribute to reduced whole-body glucose uptake. In this study, we examined the effects of iloprost - a stable prostacyclin analogue - on insulin-induced muscle capillary recruitment and whole-body glucose uptake. MATERIALS AND METHODS: In a randomized cross-over design, twelve type 2 diabetes patients (age= 55[46-69]years; BMI= 33.1[31.0-39]kg/m2 ) underwent two hyperinsulinemic-euglycemic clamps; one with and one without simultaneous low-dose iloprost infusion...
June 8, 2018: Diabetes, Obesity & Metabolism
Ashwin Singh Parihar, Shelvin Kumar Vadi, Rajender Kumar, Bhagwant Rai Mittal, Harmandeep Singh, Amanjit Bal, Rama Walia, Jaya Shukla, Saroj Kumar Sinha
Insulinomas are the most common functioning pancreatic neuroendocrine tumors and the leading cause of persistent hypoglycemia with hyperinsulinemia in adults. Glucagon-like-peptide-1 (GLP) receptor analogs are the latest agents being used in the detection of insulinomas, with initial reports suggesting high sensitivity due to universal GLP1 receptor expression on these tumors. PET/CT imaging in this patient using Ga DOTA-Exendin, a GLP receptor analog, proved useful for accurate localization of the culprit lesion, aiding in the definitive management of the patient...
June 5, 2018: Clinical Nuclear Medicine
Justin C Brown, Sui Zhang, Donna Niedzwiecki, Leonard B Saltz, Robert J Mayer, Rex B Mowat, Renaud Whittom, Alexander Hantel, Al Benson, Daniel Atienza, Michael Messino, Hedy Kindler, Alan Venook, Shuji Ogino, Yanping Li, Xuehong Zhang, Kimmie Ng, Walter C Willett, Edward L Giovannucci, Charles S Fuchs, Jeffrey A Meyerhardt
Background: Energy balance-related risk factors for colon cancer recurrence and mortality-type II diabetes, hyperinsulinemia, inflammation, and visceral obesity-are positively correlated with consumption of refined grains and negatively correlated with consumption of whole grains. We examined the relationship between the consumption of refined and whole grains with cancer recurrence and mortality in a cohort of patients with colon cancer. Methods: We conducted a prospective observational study of 1024 patients with stage III colon cancer who participated in a randomized trial of postoperative chemotherapy...
February 2018: JNCI cancer spectrum
Makoto Murata, Hitoshi Adachi, Shigeru Oshima, Masahiko Kurabayashi
Hyperglycemia is an established risk factor of coronary artery disease (CAD). However, hyperglycemia with preserved pancreatic β cell function induces hyperinsulinemia to correct the glucose profile and may even result in reactive hypoglycemia (RH), which induces an inflammatory response. In this study, the incidence of RH and its effect on arteriosclerosis were examined in CAD patients with a lengthy oral glucose tolerance test (OGTT).We performed a prospective cross-sectional study on 116 nondiabetic CAD patients [70 ± 9 years, 70% male, HbA1c < 6...
June 6, 2018: International Heart Journal
Catherine A Reardon, Amulya Lingaraju, Kelly Q Schoenfelt, Guolin Zhou, Chang Cui, Hannah Jacobs-El, Ilona Babenko, Andrew Hoofnagle, Daniel Czyz, Howard Shuman, Tomas Vaisar, Lev Becker
Type 2 diabetes (T2D) is associated with increased risk for atherosclerosis; however, the mechanisms underlying this relationship are poorly understood. Macrophages, which are activated in T2D and causatively linked to atherogenesis, are an attractive mechanistic link. Here, we use proteomics to show that diet-induced obesity and insulin resistance (obesity/IR) modulate a pro-atherogenic "macrophage-sterol-responsive-network" (MSRN), which, in turn, predisposes macrophages to cholesterol accumulation...
June 5, 2018: Cell Reports
David R Luke, Karen Ka Yan Lee, Carl W Rausch, Camille Cheng
BTI320 is a proprietary fractionated mannan polysaccharide being studied for attenuation of postprandial glucose excursion. The apparent blood glucose-lowering effect of this compound is effective in lowering postprandial hyperinsulinemia, participating in the metabolic regulation of other lipid molecules; the consequence of this activity is yet to be validated with BTI320 with respect to the risk of cardiovascular disease. The primary objective of the study was to determine the postprandial glucose and insulin responses to 3 test meals containing rice alone or consumed with BTI320 (study A) or 3 test meals (SpriteTM ) alone or consumed with BTI320 (study B)...
June 5, 2018: Clinical Pharmacology in Drug Development
Yu Guo, Wei Fu, Yakai Xin, Jinlei Bai, Huifang Peng, Liujun Fu, Jie Liu, Liping Li, Yujin Ma, Hongwei Jiang
This study is designed to investigate the effect of artemether on type 2 diabetic db/db mice. The experiments consisted of three groups: normal control (NC, db/+, 1% methylcellulose, intragastric administration), diabetic control (DM, db/db, 1% methylcellulose, intragastric administration), and artemether treated (artemether, db/db, 200 mg/kg of artemether, intragastric administration). The treatment lasted for two weeks. The food intake, body weight, and fasting blood glucose of mice were measured every three days...
2018: BioMed Research International
Masashi Tanaka, Shinya Masuda, Hajime Yamakage, Takayuki Inoue, Ryuji Ohue-Kitano, Shigefumi Yokota, Toru Kusakabe, Hiromichi Wada, Kiyoshi Sanada, Kojiro Ishii, Koji Hasegawa, Akira Shimatsu, Noriko Satoh-Asahara
AIMS: The protein myostatin is a member of the transforming growth factor β superfamily. This is mainly expressed in skeletal muscle and negatively regulates skeletal muscle growth. The present study aimed to elucidate the associations among circulating myostatin level, skeletal muscle mass, and metabolic profiles in Japanese obese patients. METHODS: Japanese obese outpatients (n = 74) were enrolled. We measured clinical parameters, quantified serum myostatin levels, and examined their associations in a cross-sectional manner...
May 30, 2018: Diabetes Research and Clinical Practice
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