title: The adipogenic potential of Cr(III). A molecular approach exemplifying metal-induced enhancement of insulin mimesis in diabetes mellitus II.
abstract: Insulin resistance is identified through numerous pathophysiological conditions, such as Diabetes mellitus II, obesity, hypertension and other metabolic syndromes. Enhancement of insulin action and\or its complete replacement by insulin-enhancing or insulin-mimetic agents seems to improve treatment of metabolic diseases. Over the last decades, intensive research has targeted the investigation of such agents, with chromium emerging as an important inorganic cofactor involved in the requisite metabolic chemistry. Chromium in its trivalent state has been shown to play a central role in carbohydrate metabolism by enhancing insulin signaling, action, and thus the sensitivity of insulin-sensitive tissues. A very likely link between diabetes and obesity is the adipose tissue, which stores energy in the form of triglycerides and releases free fatty acids. To date, there is paucity of information on the exact mechanism of the chromium effect concerning insulin-activated molecular paths, such as adipogenesis. The aim of the present study is to delve into such an effect by employing a well-defined form of chromium (Cr(III)-citrate) on the a) survival of pre- and mature adipocytes (3T3-L1), b) endogenous cell motility, and c) insulin-enhancing adipogenic capacity. The emerging results suggest that Cr(III)-citrate a) is (a)toxic in a concentration- and time-dependent manner, b) has no influence on cell motility, c) can induce 3T3-L1 pre-adipocyte differentiation into mature adipocytes through elevation of tissue specific biomarker levels (PPAR-γ, GLUT 4 and GCK), and d) exemplifies structurally-based metal-induced adipogenesis as a key process contributing to the development of future antidiabetic metallodrugs.
authors.affiliation: Laboratory of Inorganic Chemistry, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
authors.forename: O
authors.initials: O
authors.lastname: Tsave
authors.affiliation: Division of Clinical and Molecular Endocrinology, 1st Department of Internal Medicine, AHEPA, University Hospital, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
authors.forename: M P
authors.initials: MP
authors.lastname: Yavropoulou
authors.affiliation: Laboratory of Inorganic Chemistry, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Kafantari
authors.affiliation: Laboratory of Inorganic Chemistry, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece; Center for Research of the Structure of Matter, Magnetic Resonance Laboratory, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
authors.forename: C
authors.initials: C
authors.lastname: Gabriel
authors.affiliation: Division of Clinical and Molecular Endocrinology, 1st Department of Internal Medicine, AHEPA, University Hospital, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
authors.forename: J G
authors.initials: JG
authors.lastname: Yovos
authors.affiliation: Laboratory of Inorganic Chemistry, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece. Electronic address: salif@auth.gr.
authors.forename: A
authors.initials: A
authors.lastname: Salifoglou
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002857:Chromium / Q000737:chemistry / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology; D007328:Insulin / Q000737:chemistry / Q000494:pharmacology; D051379:Mice
chemical_list: D000943:Antigens, Differentiation; D007004:Hypoglycemic Agents; D007328:Insulin; D002857:Chromium
keywords: Adipocyte differentiation; Adipogenic capacity; Chromium-citrate; Insulin mimesis; Insulin-like chromium activity; Molecular biomarkers