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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The monomethyl ester of succinic acid (SME) was recently proposed as a novel tool for stimulation of proinsulin biosynthesis and insulin release in animal models of non-insulin-dependent diabetes mellitus. In the present study, either saline or SME (14 mmol/day) was infused for 3 days to control rats, animals injected with streptozotocin during the neonatal period, and Goto-Kakizaki rats with inherited diabetes. The infusion of SME failed to correct the anomalies found in the islets of diabetic rats, namely, a decreased activity of the mitochondrial FAD-linked glycerophosphate dehydrogenase, a low insulin content, and an impaired secretory response to various nutrient secretagogues including D-glucose, 2-ketoisocaproate, and the combination of L-leucine and L-glutamine. These findings raise the question of whether a more prolonged administration of SME is required to raise the insulin store and improve the secretory potential of the endocrine pancreas in animals with type 2 diabetes.
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PMID:Enzymatic and secretory activities in pancreatic islets of non-insulin-dependent diabetic rats after short-term infusion of succinic acid monomethyl ester. 771 Jul 67

The present study deals with the insulinotropic action of the dimethyl ester of succinic acid (SAD), considered as a potential tool for the treatment of non-insulin-dependent diabetes mellitus. In the perfused pancreas prepared from either euglycemic rats or animals first infused for 48 hours with a solution of D-glucose, SAD (10 mM) markedly enhanced insulin output evoked by a high concentration of D-glucose (16.7 mM), whether in the absence or presence of glimepiride (0.5 microM). The succinate ester failed, however, to affect glucagon secretion. Thus, SAD indeed displays favourable attributes for stimulation of insulin release in type 2 diabetes, with emphasis on its insulinotropic efficiency at high concentrations of D-glucose in an animal model of B-cell glucotoxicity.
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PMID:Enhancement by succinic acid dimethyl ester of insulin release evoked by D-glucose and glimepiride in the perfused pancreas of normoglycemic and hyperglycemic rats. 818 62

Selected esters of succinic acid are currently under investigation as possible insulinotropic tools in the treatment of non-insulin-dependent diabetes mellitus. Novel esters with high insulinotropic efficiency were recently synthesized. The present study concerns the effects of two of these novel esters, namely glycerol-1,2-dimethylsuccinate (2.5 mM) and propanediol-1,2-dimethylsuccinate (1.0 mM), upon the release of insulin and the de novo biosynthesis of peptides in islets from hereditarily diabetic Goto-Kakizaki rats. Whereas D-glucose (2.8 to 16.7 mM) caused a concentration-related stimulation of insulin release in the islets of the diabetic rats, the two esters of succinic acid only increased modestly, and often not significantly, insulin secretion. Nevertheless, they both markedly increased the incorporation of L-[4-3H]phenylalanine into trichloroacetic acid-precipitable material in islets deprived of any other exogenous nutrient. These findings indicate that, at variance with all pharmaceutical agents presently used or proposed as insulin secretagogues in the treatment of type 2 diabetes, glycerol-1,2-dimethylsuccinate and propanediol-1,2-dimethylsuccinate, considered as islet cell nutrients, display, in addition to their insulinotropic action, the property of stimulating biosynthetic activity in the endocrine pancreas of animals affected by this disease.
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PMID:Effects of glycerol-1,2-dimethylsuccinate and propanediol-1,2-dimethylsuccinate on insulin release and protein biosynthesis in islets of Goto-Kakizaki rats. 943 19

Succinic acid esters are currently under investigation as possible insulinotropic tools in the treatment of noninsulin-dependent diabetes mellitus. The present article introduces three novel nutrient esters and aims mainly to explore, in both normal and GK rats, the secretory response to such esters when tested alone or in combination. It documents that in pancreatic islets from normal rats, methyl acetate (10 mM), which fails to augment basal insulin output, potentiates the secretory response to succinate dimethyl ester (also 10 mM). It also reveals that alpha-D-glucose pentaacetate (alpha GPA) (1.7 mM) stimulates insulin release in the absence of any other exogenous nutrient and even more so in the presence of succinate methyl ester. Moreover, the methyl esters of succinic acid (10 mM), when used together with either methyl acetate or alpha GPA, provoked insulin secretion in islets from diabetic GK rats incubated in the absence of D-glucose, although no significant secretory response of such islets could be detected when each of these agents was tested separately. These findings thus draw attention to the insulinotropic potential in type 2 diabetes of selected combinations of nutrient esters, including a D-glucose ester presumably able to enter into islet cells without requiring the intervention of a hexose carrier.
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PMID:Synergistic insulinotropic action of succinate, acetate, and glucose esters in islets from normal and diabetic rats. 954 40

The nutritional value of glycerol-1,2,3-tris(methylsuccinate), a novel ester of succinic acid with high insulinotropic efficiency both in vitro and in vivo, was assessed in both fed and starved rats. The infusion of the ester, given in a daily amount (1.2 micromol. g body wt-1) well in excess of what could result from its repeated intravenous administration as an insulinotropic agent in non-insulin-dependent diabetes (0.07 micromol. g body wt-1 for each administration), failed to prevent the fall in body weight, liver and muscle glycogen contents, and plasma d-glucose or insulin concentration, as well as the increase in plasma free fatty acid and beta-hydroxybutyrate concentrations caused by starvation. The sole indications that the ester may serve, to a limited extent, as an alternative nutrient in starved rats consisted in a somewhat higher weight of both liver and paraovarian adipose tissue and somewhat higher activity of liver glucokinase in rats receiving the ester than in animals infused with saline. The low nutritional value of this ester thus answers the objection of its possible role as an extrapancreatic nutrient or gluconeogenic precursor in the perspective of its use as an insulinotropic tool in type 2 diabetes.
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PMID:Assessment of the nutritional value of glycerol-1,2, 3-tris(methylsuccinate) in fed and starved rats. 1038 33

Most patients with type 2 (non-insulin-dependent) diabetes mellitus require pharmacotherapy, initially as monotherapy and subsequently in combination, as adjuncts to diet and exercise. Exogenous insulin is ultimately required in a substantial proportion, reflecting the progressive natural history of the disease. Sulphonylureas and biguanides have been employed for over 4 decades as oral antidiabetic agents, but they have a limited capacity to provide long term glycaemic control and can cause serious adverse effects. Thus, more efficacious and tolerable antidiabetic agents are required. Recent years have witnessed the introduction of agents with novel modes of action, that is, the alpha-glucosidase inhibitors acarbose and miglitol (which reduce postprandial hyperglycaemia) and the first of the thiazolidinedione insulinsensitising drugs--troglitazone and rosiglitazone. Although the former has been withdrawn in some countries due to adverse effects, another 'glitazone' pioglitazone is expected to be approved in the near future. Other recently introduced drugs include glimepiride and the meglitinide insulin secretagogue, repaglinide. Attention is also focusing increasingly on combination therapy using insulin together with sulphonylureas, metformin or troglitazone. Rapid-acting insulin analogues are now being used as alternatives to conventional insulins; their role in the management of type 2 diabetes mellitus is presently uncertain but reports of a reduced frequency of hypoglycaemia are encouraging. The development of new drugs aims to counter the principal metabolic defects of the disorder, respectively, relative insulin deficiency and insulin resistance. Novel classes of rapid-acting secretagogues under evaluation include the morphilinoguanide BTS 67582 and the meglitinides mitiglinide (KAD 1229) and senaglinide (A-4166). Succinate ester derivatives represent a potential novel approach to improving beta-cell function through enhancement of insulin biosynthesis and secretion. Enhancement of nutrient-induced insulin secretion is a mechanism with several putative targets within the beta-cell; potentiators of insulin secretion include glucagon-like peptide-1 and its analogues, phosphodiesterase inhibitors and the imidazoline derivative PMS 812 (S 21663). The amylin agonist pramlintide slows gastric emptying and suppression of glucagon secretion. Non-thiazolidinedione insulin-sensitising agents include the gamma-receptor agonist G 1262570X (GG 570) and D-chiro-inositol. Insulin analogues with prolonged action and inhaled insulin preparations are also under investigation. Insulin-mimetic agents include organic vanadium compounds. Whether newer agents will offer clinically relevant efficacy and tolerability advantages over existing therapies remains to be determined.
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PMID:Recent developments and emerging therapies for type 2 diabetes mellitus. 1082 Jun 47

To investigate the influence of the succinic acid treatment on geriatric patients with type 2 diabetes. Succinic Acid has some positive biological properties. One of its is a neglecting of an aerobic glycolysis. In this study we evaluated the efficacy of the combination of the succinic acid ("MITOMIN") on treating of diabetic neuropathy of geriatric patients with type 2 diabetes. The analysis was carried out using 26 patients (aged 60-76 years). The duration of diabetes was 9.15 +/- 1.43 years. Biomedical parameters were measured by standard methods; microalbuminuria was measured by "Micral-Test". Quality of life (psychosocial disorders) was estimated with the help of "SANDOZ"-scale for geriatric assessment. The therapy was assigned 1.5 g of mitomin per day during a month. All patients were examined on having late diabetic complications: 7.69%--had diabetic retinopathy; 11.54%--diabetic nephropathy; 73.08%--diabetic neuropathy; 46.15%--chronic failure of brain vessels; 11.5%--macroangiopathy of lower extremities and 100%--had ischeamic heart disease of different levels. Mitomin therapy improved basal and postprandial glycemic control (NS), variance of pallesthesia (p < 0.001), parameters of quality of life, i.e. depression (p < 0.001), anxiety (p < 0.01), short memory (p < 0.05) and emotionality (p < 0.001). Mitomin therapy plays a positive role in management of elderly patients with type 2 diabetes. It improves glycemic control, pallestesia and quality of life. Combination of succinic acid renders central and peripheral neuropathy protective efficacy.
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PMID:[Diabetes mellitus in the elderly: succinic acid compounds in treating diabetic neuropathies]. 1209 44

Esters of succinic acid are potent insulin secretagogues, and have been proposed as novel antidiabetic agents for type 2 diabetes. This study examines the effects of acute and chronic exposure to succinic acid monomethyl ester (SAM) on insulin secretion, glucose metabolism and pancreatic beta cell function using the BRIN-BD11 cell line. SAM stimulated insulin release in a dose-dependent manner at both non-stimulatory (1.1 mM) and stimulatory (16.7 mM) glucose. The depolarizing actions of arginine also stimulated a significant increase in SAM-induced insulin release but 2-ketoisocaproic acid (KIC) inhibited SAM induced insulin secretion indicating a possible competition between the preferential oxidative metabolism of these two agents. Prolonged (18 hour) exposure to SAM revealed decreases in the insulin-secretory responses to glucose, KIC, glyceraldehyde and alanine. Furthermore, SAM diminished the effects of non-metabolized secretagogues arginine and 3-isobutyl-1-methylxanthine (IBMX). While the ability of BRIN-BD11 cells to oxidise glucose was unaffected by SAM culture, glucose utilization was substantially reduced. Collectively, these data suggest that while SAM may enhance the secretory potential of non-metabolized secretagogues, it may also serve as a preferential metabolic fuel in preference to other important physiological nutrients and compromise pancreatic beta cell function following prolonged exposure.
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PMID:Differential acute and long term actions of succinic acid monomethyl ester exposure on insulin-secreting BRIN-BD11 cells. 1236 22

We describe a case of a 58-year-old male with longstanding hypertension and Type 2 diabetes mellitus who developed sudden onset renal impairment. The first clue to the possible presence of amyloidosis in this case was provided by the radionuclide renal cortical scan performed with trivalent dimercapto succinic acid (Tc99m-DMSA-3), which revealed intense tracer uptake in the spleen suggesting amyloid deposit. Further workup to ascertain the cause of amyloidosis led to the diagnosis of multiple myeloma. We conclude that in cases of extra-renal or splenic accumulation of Tc99m-DMSA-3, a diagnosis of amyloidosis should be considered, in an appropriate clinical setting.
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PMID:Accumulation of Tc99m-DMSA-3 in the spleen in a case of multiple myeloma with associated amyloidosis. 1600 4

Succinic acid mono ethyl ester (EMS) was recently proposed as an insulinotropic tool in the treatment of non-insulin dependent diabetes mellitus. The aim of this study was to investigate the effect of EMS on oxidative stress in a streptozotocin (STZ)-nicotinamide induced type 2 diabetic model. The EMS was injected intraperitoneally at 8 micro mol/g body weight for 30 days. Plasma glucose, plasma insulin, thiobarbituricacid reactive substances (TBARS), hydroperoxides, superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (Gpx), reduced glutathione (GSH), glutathione-S-transferase (GST), and vitamins C and E were assayed in liver and kidney. Treatment with EMS and metformin to diabetic rats resulted in a significant reduction in plasma glucose, TBARS, and hydroperoxides. In addition, the treated groups also showed a significant increase in the activities of plasma insulin, SOD, CAT, GPx, GST, GSH, vitamin C, and vitamin E in liver and kidney of STZ-nicotinamide-induced diabetic rats. Our result suggest that non glucidic nutrient, such as EMS as a potent antidiabetic, may optimalize antiperoxidative and antioxidants status by restoring the biochemical alterations found in STZ-nicotinamide-induced type 2 diabetes.
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PMID:Succinic acid monoethyl ester prevents oxidative stress in streptozotocin-nicotinamide-induced type2 diabetic rats. 1691 Mar 16


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