naphthoquinones and Diabetes-Mellitus--Type-2

Diabetes mellitus is a systemic disease responsible for morbidity in the western world and is gradually becoming prevalent in developing countries too. The prevalence of diabetes is rapidly increasing in industrialized countries and type 2 diabetes accounts for 90% of the disease. Insulin resistance is a major pathophysiological factor in the development of type 2 diabetes, occurring mainly in muscle, adipose tissues, and liver leading to reduced glucose uptake and utilization and increased glucose production. The prevalence and rising incidence of diabetes emphasized the need to explore new molecular targets and strategies to develop novel antihyperglycemic agents. Protein Tyrosine Phosphatase 1B (PTP 1B) has recently emerged as a promising molecular level legitimate therapeutic target in the effective management of type 2 diabetes. PTP 1B, a cytosolic nonreceptor PTPase, has been implicated as a negative regulator of insulin signal transduction. Therefore, PTP 1B inhibitors would increase insulin sensitivity by blocking the PTP 1B-mediated negative insulin signaling pathway and might be an attractive target for type 2 diabetes mellitus and obesity. With X-ray crystallography and NMR-based fragment screening, the binding interactions of several classes of inhibitors have been elucidated, which could help the design of future PTP 1B inhibitors. The drug discovery research in PTP 1B is a challenging area to work with and many pharmaceutical organizations and academic research laboratories are focusing their research toward the development of potential PTP 1B inhibitors which would prove to be a milestone for the management of diabetes.

Topics: Acetophenones; Amino Acid Sequence; Animals; Benzoates; Benzofurans; Biphenyl Compounds; Blood Glucose; Catalytic Domain; Catechols; Chromones; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Fluorides; Humans; Insulin; Insulin Resistance; Insulin Secretion; Janus Kinase 2; Models, Molecular; Naphthoquinones; Peptidomimetics; Phosphates; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Pyridazines; Receptor, Insulin; Signal Transduction; STAT3 Transcription Factor; Thiazoles; Thiazolidinediones; Thiophenes; Vanadium Compounds

Inositol pyrophosphates (PP-InsPs) are energetic signaling molecules with important functions in mammals. As their biosynthesis depends on ATP concentration, PP-InsPs are tightly connected to cellular energy homeostasis. Consequently, an increasing number of studies involve PP-InsPs in metabolic disorders, such as type 2 diabetes, aspects of tumorigenesis, and hyperphosphatemia. Research conducted in yeast suggests that the PP-InsP pathway is activated in response to reactive oxygen species (ROS). However, the precise modulation of PP-InsPs during cellular ROS signaling is unknown. Here, we report how mammalian PP-InsP levels are changing during exposure to exogenous (H

Topics: Adenosine Triphosphate; Cell Line, Tumor; Diabetes Mellitus, Type 2; Diphosphates; Humans; Hydrogen Peroxide; Inositol; NAD(P)H Dehydrogenase (Quinone); Naphthoquinones; Oxygen; Reactive Oxygen Species

Diabetes mellitus is one of the most public metabolic disorders. It is mainly classified into type 1 and type 2. Echinochrome is a pigment from sea urchins that has antioxidant, anti-microbial, anti-inflammatory and chelating abilities.. The present study aimed to investigate the anti-diabetic mechanisms of echinochrome pigment in streptozotocin-induced diabetic rats.. Thirty six male Wistar albino rats were divided into two main groups, type 1 diabetes and type 2 diabetes groups. Each group was divided into 3 subgroups (6 rats/subgroup); control, diabetic and echinochrome groups. Diabetic model was induced by a single dose of streptozotocin (60mg/kg, i.p) for type 1 diabetes and by a high fat diet for 4weeks before the injection with streptozotocin (30mg/kg, i.p) for type 2 diabetes. Diabetic groups were treated orally with echinochrome extract (1mg/kg body weight in 10% DMSO) daily for 4weeks.. Echinochrome groups showed a reduction in the concentrations of glucose, MDA and the activities of arginase, AST, ALT, ALP and GGT. While it caused general increase in the levels of insulin, TB, DB, IB, NO and the activities of G6PD, GST, GPx, SOD and GSH. The histopathological investigation showed partial restoration of pancreatic islet cells and clear improvement in the hepatic architecture.. The suggested mechanism of Ech action in the reduction of diabetic complications in liver involved two pathways; through the hypoglycemic activity and the antioxidant role of Ech.

Topics: Animals; Blood Glucose; Diabetes Complications; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diet, High-Fat; Islets of Langerhans; Liver Diseases; Liver Function Tests; Male; Malondialdehyde; Naphthoquinones; Oxidative Stress; Rats; Rats, Wistar

Chemical investigation of the Western Australian marine brown alga Cystophora harveyi resulted in the isolation of the new linearly fused 6,6,5-tricyclic compound pycnanthuquinone C (1), in addition to four previously reported geranyltoluquinol derivatives. Structures were elucidated by interpretation of spectrometric data. Compounds with the same cyclic skeleton as 1 have been reported to be useful drug leads for the treatment of type 2 diabetes, while compounds 4 and 7 are known constituents of Chinese medicinal herbs. A biosynthetic scheme encompassing all of the geranyltoluquinol derivatives isolated from C. harveyi is proposed.

Topics: Diabetes Mellitus, Type 2; Drugs, Chinese Herbal; Fatty Acids, Unsaturated; Marine Biology; Molecular Structure; Naphthoquinones; Phaeophyceae; Terpenes; Western Australia

Using an ethnomedical-based drug discovery program, two previously unknown compounds (SP-18904 and SP-18905) from Pycnanthus angolensis were isolated that lower glucose concentrations in mouse models of type 2 diabetes. SP-18904 and SP-18905 are terpenoid-type quinones that significantly lowered plasma glucose concentration (p <.05) when given orally to either ob/ob or db/db mice, both of which are hyperglycemic and hyperinsulinemic. The antihyperglycemic actions of SP-18904 and SP-18905 were associated with significant decreases in plasma insulin concentrations (p <.05), suggesting that both compounds lowered glucose by enhancing insulin-mediated glucose uptake. This was supported by the insulin suppression test in ob/ob mice. Studies in hyperglycemic, insulin-deficient mice and in vitro experiments on 3T3-L1 adipocytes further supported this conclusion. As such, these two terpenoid-type quinones represent a new class of compounds of potential use in the treatment of type 2 diabetes.

Topics: Adipocytes; Animals; Blood Glucose; Cells, Cultured; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Disease Models, Animal; Eating; Hypoglycemic Agents; Insulin; Male; Mice; Mice, Inbred C57BL; Naphthoquinones; Plant Extracts; Plants, Medicinal; Trees