title: Molecular mechanisms involved in lead induced disruption of hepatic and pancreatic glucose metabolism.
abstract: Lead (Pb) is a toxic heavy metal known to be associated with pathology of various human chronic diseases. This study has focused on the effect of lead on glucose homeostasis with regard to metabolic function of pancreas and liver. Islets of Langerhans were isolated from the pancreas of rats and exposed to lead for 24h, then insulin release along with markers of ER stress and oxidative stress were evaluated. In another part, lead was administered to rats for 32 days and after evaluating criteria of diabetes, the activity of gluconeogenesis and glycogenolysis enzymes, and markers of oxidative stress and inflammation were measured in the liver. Lead disrupted insulin secretory function of islets through activating GSK-3β and ER stress, and increased activity of gluconeogenic enzymes in the liver featured by glucose intolerance. Chronic exposure to lead can disrupt glucose homeostasis by affecting pancreas and liver mainly through induction of insulin resistance.
authors.affiliation: School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran; Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Sara
authors.initials: S
authors.lastname: Mostafalou
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Baeeri
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran; International Campus, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Haji
authors.initials: H
authors.lastname: Bahadar
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Soltany-Rezaee-Rad
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Gholami
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: Mohammad@TUMS.Ac.Ir.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Abdollahi
mesh_terms: D000818:Animals; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009942:Organometallic Compounds / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D005952:Glucose-6-Phosphatase; C582554:Pck1 protein, rat; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D005947:Glucose; C008261:lead acetate
keywords: Diabetes; Glucose homeostasis; Insulin resistance; Lead (Pb); Liver; Pancreatic islets