The adipogenic potential of Cr(III). A molecular approach exemplifying metal-induced enhancement of insulin mimesis in diabetes mellitus II

• Published in: Journal of inorganic biochemistry Vol. 163; pp. 323 - 331
• Main Authors: Tsave, O., Yavropoulou, M.P., Kafantari, M., Gabriel, C., Yovos, J.G., Salifoglou, A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2016
• Subjects: 3T3-L1 Cells; Adipocyte differentiation; Adipocytes - metabolism; Adipogenic capacity; Animals; Antigens, Differentiation - metabolism; Biomimetic Materials - chemistry; Biomimetic Materials - pharmacology; Cell Differentiation - drug effects; Chromium - chemistry; Chromium - pharmacology; Chromium-citrate; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - pharmacology; Insulin - chemistry; Insulin - pharmacology; Insulin mimesis; Insulin-like chromium activity; Mice; Molecular biomarkers; Adipocyte differentiation; Chromium-citrate; Adipogenic capacity; Molecular biomarkers; Insulin mimesis; Insulin-like chromium activity
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2016.07.015

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. Confronting the challenge of insulin mimesis in Diabetes mellitus II prompted perusal of Cr(III)-citrate adipogenetic potential in 3T3-L1 cells. Well-defined Cr(III) species rises atoxic and starkly efficient toward adipocyte differentiation-maturation. Migration studies attest to atoxicity, with key molecular targets involved in unique Cr(III)-linked insulin-enhancement of adipocyte activity reducing hyperglycemia. [Display omitted] •Binary, atoxic, bioavailable Cr(III)-citrate induces preadipocyte differentiation.•Cr(III)-induced adipogenetic activity correlates with key genetic loci activation.•Molecular targets emerge in insulin mimetic metal-induced adipogenesis.•Cr(III) enhancement of insulin adipogenetic potential in 3T3-L1 adipocytes•Glycokinase attests to functional status of Cr(III)-induced adipocyte maturation.