Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ANTIDIABETICS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources
PubMed2005

A new orally active antidiabetic vanadyl complex--bis(alpha-furancarboxylato)oxovanadium(IV).

Bis(alpha-furancarboxylato)oxovanadium(IV)--a new orally active antidiabetic vanadyl complex has been synthesized, characterized, and tested for bioactivity as insulin-enhancing agents. The complex was administered intragastrically to both normal and STZ-diabetic rats for 4 weeks. The results show that the complex at a dose of 10.0 and 20.0 mg V kg(-1), could significantly lower the blood glucose level rats and ameliorated impaired glucose tolerance in STZ-diabetic, but not in normal rats. It was suggested that the complex exerted an antidiabetic effect in STZ-diabetic rats, which maybe was related to increasing the sensitivity to insulin.

Administration, Oral↗
PubMed2005

Compendium of the antidiabetic effects of supranutritional selenate doses. In vivo and in vitro investigations with type II diabetic db/db mice.

In recent years, a number of investigations on the antidiabetic effects of supranutritional selenate doses have been carried out. Selenate (selenium oxidation state +VI) was shown to possess regulatory effects on glycolysis, gluconeogenesis and fatty acid metabolism, metabolic pathways which are disturbed in diabetic disorders. An enhanced phosphorylation of single components of the insulin signalling pathway could be shown to be one molecular mechanism responsible for the insulinomimetic properties of selenate. In type II diabetic animals, a reduction of insulin resistance could be shown as an outcome of selenate treatment. The present study with db/db mice was performed to investigate the antidiabetic mechanisms of selenate in type II diabetic animals. Twenty-one young adult female db/db mice were randomly assigned to three experimental groups (selenium deficient=0Se, selenite-treated group=SeIV and selenate-treated group=SeVI) with seven animals each. Mice of all groups were fed a selenium-deficient diet for 8 weeks. The animals of the groups SeIV and SeVI were supplemented with increasing amounts of sodium selenite or sodium selenate up to 35% of the LD50 in week 8 in addition to the diet by tube feeding. Selenate treatment reduced insulin resistance significantly and reduced the activity of liver cytosolic protein tyrosine phosphatases (PTPs) as negative regulators of insulin signalling by about 50%. In an in vitro inhibition test selenate (oxidation state +VI) per se did not inhibit PTP activity. In this test, however, selenium compounds of the oxidation state +IV were found to be the actual inhibitors of PTP activity. Selenate administration in vivo further led to characteristic changes in the selenium-dependent redox system, which could be mimicked in an in vitro assay and provided further evidence for the intermediary formation of SeIV metabolites. The expression of peroxisome proliferator-activated receptor gamma (PPARgamma), another important factor in the context of insulin resistance and lipid metabolism, was significantly increased by selenate application. In particular, liver gluconeogenesis and lipid metabolism were influenced strongly by selenate treatment. In conclusion, our results showed that supranutritional selenate doses influenced two important mechanisms involved in insulin-resistant diabetes, namely, PTPs and PPARgamma, which, in turn, can be assumed as being responsible for the changes in intermediary metabolism, e.g., gluconeogenesis and lipid metabolism. The initiation of these mechanisms thereby seems to be coupled to the intermediary formation of the selenium oxidation state +IV (selenite state) from selenate.

Animals↗
PubMed2005

Effects on immune response of antidiabetic ingredients from white-skinned sweet potato (Ipomoea batatas L.).

OBJECTIVES: The present report describes the effects of antidiabetic ingredients from white-skinned sweet potato (AWSSP) on the immune response of human cells. METHODS: We studied the effects of inactive Staphylococcus aureus cells coated with AWSSP on phagocytic activity, phagosome-lysosome fusion, and superoxide anion release by human leukocytes in vitro. RESULTS: AWSSP increased phagocytic activity and phagosome-lysosome fusion in neutrophils and monocytes in a dose-dependent manner. In contrast, AWSSP had no significant effect on superoxide anion release (O2-) from human neutrophils. CONCLUSIONS: These results show that AWSSP is useful in the prevention and improvement of diabetic symptoms by stimulating human immunity and that Ipomoea batatas L. is a beneficial food because it increases immune activity in addition to its antidiabetic effects.

Cell Fusion↗
PubMed1989

Characteristics of non-insulin-dependent diabetic patients with secondary failure to oral antidiabetic therapy.

PURPOSE: Secondary failure to treatment with oral antidiabetic agents frequently occurs in patients with non-insulin-dependent diabetes mellitus. In the search for causes of such failures, we examined patient- and disease-related factors in nonresponders and in responders to treatment with oral antidiabetic agents. PATIENTS AND METHODS: The study population consisted of three groups: (1) 34 nonresponders to treatment with sulfonylureas; (2) 25 patients who still responded to treatment with sulfonylureas; and (3) 10 age-matched healthy control subjects. In addition to patient-related factors such as adherence to diet and knowledge of diabetes, we examined insulin response to a test meal and hepatic and peripheral insulin sensitivity during a euglycemic insulin clamp in combination with indirect calorimetry and infusion of [3H-3-]glucose. RESULTS: Patient-related factors such as daily nutrient intake, activity score, knowledge of diabetes, and "stress level" were similar in both groups. However, nonresponders had a higher rate of basal hepatic glucose production (4.60 +/- 0.14 versus 3.63 +/- 0.26 mg/minute/kg of lean body weight; p less than 0.001), which was less suppressed by euglycemic hyperinsulinemia (about 100 microU/mL) than was that of the responders (p less than 0.001). In addition, total insulin-stimulated glucose metabolism was reduced (5.07 +/- 0.22 versus 7.09 +/- 0.56 mg/kg.LBM.minute; p less than 0.001), and this was mainly accounted for by a reduction in non-oxidative glucose metabolism (glycogen synthesis and anaerobic glycolysis) (1.78 +/- 0.22 versus 3.54 +/- 0.49 mg/kg.LBM.minute; p less than 0.001). The severity of hepatic and peripheral insulin resistance correlated with the plasma glucose concentration but was unrelated to insulin secretion. In a multiple linear regression analysis, glucose overproduction in the liver (26.1%), impaired peripheral glucose metabolism (17.3%), and insulin deficiency (12.6%) could explain only 56% of the causes of secondary drug failure. CONCLUSION: Secondary failure to treatment with oral hypoglycemic agents is determined by the disease itself rather than by patient-related factors. Treatment of secondary drug failure should therefore aim at ameliorating both hepatic and peripheral insulin resistance.

Blood Glucose↗
PubMed1997

Intracellular targets for antidiabetic sulfonylureas and potassium channel openers.

Antidiabetic sulfonylureas and potassium channel openers affect the activity of the ATP-regulated potassium channel (K(ATP) channel) present in the plasma membrane of various cells. This causes a broad spectrum of physiological responses, including the modulation of insulin release from pancreatic B-cells and the relaxation of smooth muscle. Recently, new targets for antidiabetic sulfonylureas and potassium channel openers were found in membranes of organelles, such as mitochondria and zymogen- and insulin-containing granules. By acting on these targets, the drugs modulate, independently of K(ATP) channel activity, insulin release from pancreatic B-cells, and they regulate K+ transport in mitochondria and zymogen granules. The interaction of sulfonylureas and potassium channel openers with intracellular targets gives additional basic information about their properties. Additionally, these studies could be important because of the medical applications of sulfonylureas and potassium channel openers.

Adenosine Triphosphate↗
PubMed1997

Disparate effects of antidiabetic drugs on arterial contraction.

Type II diabetic patients and others with insulin resistance are at risk for development of hypertension characterized by elevated peripheral vascular resistance and loss of insulin's normal vasodilating activity. Oral antidiabetic drugs have recently been recognized to have disparate effects on arterial pressure in such patients and in related rodent models. Sulfonylureas (e.g., glyburide), which stimulate insulin secretion, have been reported either to increase or not to affect arterial pressure, whereas nonsulfonylurea agents with insulin-sensitizing properties, the biguanide metformin and various thiazolidinediones (eg, pioglitazone), have been reported to decrease arterial pressure in humans and rodents. To help elucidate these disparate effects, we investigated these agents for direct actions on arterial vascular contractility and its sensitivity to insulin. Preincubation of intact rat tail arterial tissue rings for 2 hours with known therapeutically effective antidiabetic concentrations of metformin and pioglitazone significantly attenuated the force of contractions produced by either potassium (membrane depolarization) or norepinephrine ([NE] adrenergic receptor activation). Glyburide did not influence these contractions. Preincubation with metformin also induced an attenuating (vasodilating-like) action of insulin on arterial tissue rings contracted by potassium. Conversely, glyburide induced an accentuating action of insulin on potassium-mediated contractions. These results are consistent with measures of vascular function obtained in the past after oral administration of the drugs, which suggested but did not prove that they may exert direct effects on arterial vascular contractility. Thus, metformin and thiazolidinediones may decrease arterial pressure partly by direct vasorelaxant mechanisms, with metformin having an additional effect of inducing vasorelaxation by insulin. In contrast, sulfonylureas may directly induce a paradoxical vasoconstrictor response to insulin.

Animals↗
PubMed1999

BM 17.0744: a structurally new antidiabetic compound with insulin-sensitizing and lipid-lowering activity.

BM 17.0744 (2,2-dichloro-12-(p-chlorophenyl)-dodecanoic acid) is a substance from a group of omega-substituted alkyl carboxylic acids with the general formula, ring-spacer-carboxylic acid. With BM 17.0744-a compound structurally unrelated to thiazolidinediones--antihyperglycemic and antihyperinsulinemic potency has been demonstrated in various animal models of type II diabetes. The antidiabetic effect is independent of the genetic background of the disease, gender, and animal species. The 24-hour blood glucose profile was dose- and time-dependently improved in ob/ob mice after a single and fourth oral administration of 0.3, 1, and 3 mg/kg/d. A dose-dependent reduction of hyperglycemia (10%, 15%, 28%, and 66%) was found in db/db mice after the fifth oral administration of 3, 10, 30, and 100 mg/kg/d. Hyperinsulinemia was reduced dose-dependently in yellow KK mice by 1%, 24%, 34%, and 66% after the fifth oral administration of 0.3, 1, 3, and 10 mg/kg/d. Overall glucose metabolism was predominantly higher in euglycemic-hyperinsulinemic clamp studies in obese fa/fa rats pretreated for 14 days with 10 mg/kg/d BM 17.0744. The data in diabetic and insulin-resistant animals suggest an improvement of insulin action that is supported by enhancement of insulin effects in vitro. There is no evidence of a risk for hypoglycemia in diabetic and metabolically healthy animals. Triglyceride (TG) and cholesterol were reduced in the serum of metabolically healthy rats, as well as serum lipids in db/db mice, which suggests this effect is independent of amelioration of the diabetic status. Lipid-lowering effects in diabetic and healthy animals show an additional property of BM 17.0744. Because of its antidiabetic and lipid-lowering potency, the substance is of great interest in treating the metabolic syndrome. Lipid decreases in rats are associated with a dose-dependent increase in carnitine acetyltransferase activity in the liver to about 100-fold (12.5 mg/kg/d). This together with hepatomegaly in small rodents may indicate peroxisomal proliferation, a phenomenon considered species-specific. Its relevance for humans is well documented for other classes of compounds including fibrates. Specific side effects of insulin sensitizers of the thiazolidinedione type, such as an increase in body weight and heart weight, could not be observed after 4-week oral application of BM 17.0744 in rats. In general, BM 17.0744 was well tolerated in the pharmacological dose range in all species tested.

Adipocytes↗
PubMed2002

Structure-dependent metallokinetics of antidiabetic vanadyl-picolinate complexes in rats: studies on solution structure, insulinomimetic activity, and metallokinetics.

The insulinomimetic effect of vanadium is the most remarkable and important among its several biological actions. Vanadyl ion (+4 oxidation state of vanadium) and its complexes have been found to normalize the blood glucose levels of both type 1 and 2 diabetic animals. We have developed insulinomimetic vanadyl complexes having different coordination modes, emphasizing the possible usefulness of vanadyl-picolinate [VO(pa)(2)] and its related complexes with the VO(N(2)O(2)) coordination mode. In order to apply these complexes clinically in the future, the relationship between the chemical structure, insulinomimetic action, organ distribution of vanadium, and blood disposition of vanadyl species must be closely investigated. In the present investigation, we studied the blood disposition of the vanadyl-picolinate complexes in healthy rats, and tried to understand comprehensively the relationship between the structures, insulinomimetic activity, and metallokinetic parameters of the complexes, which had been recently prepared and specifically synthesized for the present study, by using an in vivo blood circulation monitoring -- electron spin resonance (BCM-ESR) method for analyzing ESR signals due to paramagnetic metal ions and complexes in the blood in real time. Metallokinetic parameters were estimated based on the blood clearance curves in terms of a two-compartment pharmacokinetic model, and vanadyl species were indicated to be distributed in peripheral tissues and gradually eliminated from the circulating blood, depending on their chemical structures. Vanadyl concentrations in the blood of rats given bis(5-iodopicolinato)oxovanadium(IV) [VO(5ipa)(2)] and bis(3-methylpicolinato)oxovanadium(IV) [VO(3mpa)(2)] with electron-withdrawing and donating groups, respectively, remained significantly higher and longer, due to their slower clearance rates from the blood, than in rats given other complexes, suggesting that the high exposure and long residence of vanadyl species bring about the high normoglyceric effect in diabetic animals. We then examined the relationship between insulinomimetic activity and metallokinetic parameters in the family of VO(pa)(2) for further development of insulinomimetic vanadyl complexes. IC(50), the 50% inhibitory concentration of the complexes on the free fatty acid release from isolated rat adipocytes treated with epinephrine, was found to be sufficiently correlated with metallokinetic parameters such as area under the concentration curve, mean residence time, total clearance, and distribution volume at steady-state. Furthermore, the in vivo antidiabetic activity of the complexes was enhanced with increasing exposure and residence of vanadyl species in the blood of animals. On the basis of these results, we concluded that in vitro insulinomimetic activity, metallokinetic character, and in vivo antidiabetic action of vanadyl-picolinate complexes are closely related to their chemical structures.

Adipocytes↗
PubMed2003

Antidiabetic activity of Terminalia catappa Linn fruits.

In view of alleged antidiabetic potential, effect of the petroleum ether, methanol, and aqueous extracts of Terminalia catappa Linn (combretaceae) fruit, on fasting blood sugar levels and serum biochemical analysis in alloxan-induced diabetic rats were investigated. All the three extracts of Terminalia catappa produced a significant antidiabetic activity at dose levels 1/5 of their lethal doses. Concurrent histological studies of the pancreas of these animals showed comparable regeneration by methanolic and aqueous extracts which were earlier, necrosed by alloxan.

Alloxan↗
PubMed2002

Antidiabetic effect of a nitrosamine-free dephostatin analogue, methoxime-3,4-dephostatin, in db/db mice.

Et-3,4-dephostatin, a protein-tyrosine phosphatase (PTPase) inhibitor, potentiates insulin-dependent signal transduction and shows an antidiabetic effect in mice. However, it contains a nitrosamine moiety that is often mutagenic and carcinogenic. Therefore, we previously designed and synthesized methoxime-3,4-dephostatin as a nitrosamine-free analogue of dephostatin. In the present paper, we studied in situ and in vivo antidiabetic effects of this PTPase inhibitor. Methoxime-3,4-dephostatin induced 2-deoxyglucose transport by mouse 3T3-L1 adipocytes and rat L6 myocytes without insulin. It also inhibited glucagon-induced glucose release from primary culture rat hepatocytes. When hepatocytes were prepared from starved rats, methoxime-3,4-dephostatin did not inhibit the release of glucose, indicating that the chemical may act on glycogenolysis. Oral administration of methoxime-3,4-dephostatin for 3-7 days inhibited the increase in the blood glucose level in type-2 diabetes model db/db mice. It also decreased food and water intakes of mice, but showed no liver or blood toxicity.

3T3 Cells↗
PubMedDate not supplied

Participation of high glucose concentrations in neutrophil adhesion and surface expression of adhesion molecules on cultured human endothelial cells: effect of antidiabetic medicines.

BACKGROUND: Atherosclerosis and vascular inflammation induced by hyperglycemia are important factors in the promotion of diabetic complications. One of the earliest events in the inflammatory process is increased binding of neutrophils to endothelial cells. Since vascular inflammation has been recently reported to be crucial for the onset of atherosclerosis-mediated serious diseases (acute myocardial infarction, stroke), in this study, we examined the effects of high glucose concentrations on endothelial-neutrophil cell adhesion and surface expression of endothelial adhesion molecules. We also evaluated the effects of various antidiabetic medicines on these events. METHODS: Human umbilical vein endothelial cells (HUVECs) were first cultured for 48 h in the glucose-rich medium, and neutrophils from healthy volunteers were then added and allowed to adhere for 30 min. Adhered neutrophils were quantified by measuring myeloperoxidase (MPO) activities, and surface expression of endothelial adhesion molecules was determined using an enzyme immunoassay. RESULTS: High glucose concentrations (over 27.8 mM) increased endothelial-neutrophil cell adhesion and expression of endothelial adhesion molecules (intercellular adhesion molecule-1 (ICAM-1), P-selectin, E-selectin). These events were protein kinase C (PKC) dependent, because PKC inhibitors, but not other intracellular second messenger inhibitors, significantly blocked them. Among antidiabetic medicines, a sulfonylurea, gliclazide (but not glibenclamide or glimepiride), and an aldose reductase inhibitor, epalrestat, significantly inhibited these events; however, a new K(ATP)-channel blocker, netegulinide, a biguanide, metformine, or an insulin sensitizer, troglitazone, did not. CONCLUSIONS: Our data is consistent with hyperglycemia-mediated vascular inflammation through increases in neutrophil adhesion and expression of endothelial adhesion molecules. These events might lead to the onset of atherosclerosis-mediated serious diseases, but could be inhibited by something perhaps, such as gliclazide and epalrestat.

Carbazoles↗
PubMedDate not supplied

The pathophysiologic basis of efficacy and clinical experience with the new oral antidiabetic agents.

Type 2 diabetes results from the abnormal resistance of peripheral tissues to insulin and from the progressive insulin secretory failure of the pancreatic beta-cells. Treatment of type 2 diabetes has greatly improved due to the availability of new classes of oral antidiabetic drugs (OADs) and new insulin analogs. Three types of oral medications exert their antidiabetic action without directly stimulating insulin release: alpha-glucosidase inhibitors (e.g., acarbose) interfere with the digestion of dietary glucose precursors and the absorption of glucose; biguanides (e.g., metformin) inhibit hepatic gluconeogenesis, thereby lowering fasting blood glucose concentrations and increasing peripheral insulin sensitivity; and thiazolidinediones (e.g., rosiglitazone) improve the sensitivity of tissues to insulin-stimulated glucose disposal. In contrast, two classes of OADs stimulate insulin release from pancreatic beta-cells. Sulfonylureas (e.g., glyburide) have been used successfully for many years to treat type 2 diabetes, but their prolonged action may result in hypoglycemia. The third-generation sulfonylurea glimepiride is associated with a reduced risk of hypoglycemia and less weight gain than other sulfonylureas. Finally, the meglitinides (e.g., repaglinide) and D-phenylalanine derivatives (e.g., nateglinide) are powerful prandial insulin secretagogues. If the pancreatic beta-cells deteriorate to such an extent that insulin secretion is significantly impaired, treatment with additional exogenous insulin may be required.

Administration, Oral↗
PubMed2001

Synthesis and biological activity of analogues of the antidiabetic/antiobesity agent 3-guanidinopropionic acid: discovery of a novel aminoguanidinoacetic acid antidiabetic agent.

3-Guanidinopropionic acid (1, PNU-10483) has been demonstrated to both improve insulin sensitivity and to promote weight loss selectively from adipose tissue in animal models of non-insulin-dependent diabetes mellitus (NIDDM). However, 1 has also been shown to be a substrate for both the creatine transporter and creatine kinase, leading to marked accumulation in muscle tissue as the corresponding N-phosphate 4. In an effort to identify novel entities that maintain antidiabetic potency without susceptibility to creatine-like metabolism, an analogue program was undertaken to explore the effects of various structural modifications, including homologation, simple substitution, single atom mutations, and bioisosteric replacements for the guanidine and carboxylic acid. Overall, the scope of activity encompassed by the set of new analogues proved to be exceedingly narrow. Notable exceptions demonstrating equivalent or improved antidiabetic activity included the alpha-amino derivative 29, aminopyridine 47, isothiourea 67, and aminoguanidine 69. On the basis of its superior therapeutic ratio, aminoguanidine 69 was selected for preclinical development and became the foundation for a second phase of analogue work. Furthermore, in vitro studies demonstrated that 69 is markedly less susceptible to phosphorylation by creatine kinase than the lead 1, suggesting that it should have less potential for accumulation in muscle tissue than 1.

Acetates↗
PubMed2003

Discovery of a long-chain carbamoyl aminocarnitine derivative, a reversible carnitine palmitoyltransferase inhibitor with antiketotic and antidiabetic activity.

The synthesis and pharmacological activity of reversible CPT I inhibitors as potential antiketotic and antidiabetic drugs are reported. Such inhibitors constitute a series of enantiomerically pure aminocarnitine derivatives having the general formula (CH3)3N+CH2CH(ZR)CH2COO- (with Z = ureido, carbamate, sulfonamide, and sulfamide moieties; R = C7-C14 linear alkyl chains). A primary pharmacological screening based on the evaluation of CPT I activity in intact rat liver (L-CPT I) mitochondria revealed the best activity for the (R) forms of ureidic derivative 17 (ZR = NHCONHR, R = C14), sulfonamidic derivative 7 (ZR = NHSO2R, R = C12), and sulfamidic derivative 9 (ZR = NHSO2NHR, R = C11). The IC50 values are 1.1, 0.7, and 0.8 microM, respectively. For the carbamic derivative 11 (ZR = NHCOOR, R = C8), an IC50 of 9.5 microM was observed. In addition, an extraordinarily high selectivity toward the liver isoform with respect to the heart isoform (muscle-CPT I identical with M-CPT I) was found for the ureidic compound 17 (IC50(M-CPT I) vs IC50(L-CPTI) = 39.4), as well as for other ureidic or carbamic compounds. Diabetic db/db mice treated orally with 17 and 7 for 45 days at a dose of 50 mg/kg twice a day showed a good reduction of serum glucose levels with respect to the untreated db/db mice (p < 0.01). In addition, 17 showed antiketotic activity in normal fasted rats. 17 has been selected for development as a potential antiketotic and antidiabetic drug.

3-Hydroxybutyric Acid↗
PubMed2000

Induced desensitization of the insulinotropic effects of antidiabetic drugs, BTS 67 582 and tolbutamide.

Acute and chronic mechanisms of action of novel insulinotropic antidiabetic drug, BTS 67 582 (1, 1-dimethyl-2-(2-morpholinophenyl)guanidine fumarate), were examined in the stable cultured BRIN-BD11 cell line. BTS 67 582 (100 - 400 microM) stimulated a concentration-dependent increase (P<0.01) in insulin release at both non-stimulatory (1.1 mM) and stimulatory (8. 4 mM) glucose. Long-term exposure (3 - 18 h) to 100 microM BTS 67 582 in culture time-dependently decreased subsequent responsiveness to acute challenge with 200 microM BTS 67 582 or 200 microM tolbutamide at 12 - 18 h (P<0.001). Similarly 3 - 18 h culture with the sulphonylurea, tolbutamide (100 microM), also effectively suppressed subsequent insulinotropic responses to both BTS 67 582 and tolbutamide. Culture with 100 microM BTS 67 582 or 100 microM tolbutamide did not affect basal insulin secretion, cellular insulin content, or cell viability and exerted no influence on the secretory responsiveness to 200 microM of the imidazoline, efaroxan. While 18 h BTS 67 582 culture did not affect the insulin-releasing actions (P<0.001) of 16.7 mM glucose, 10 mM arginine, 30 mM KCl, 25 microM forskolin or 10 nM phorbol-12-myristate 13-acetate (PMA), significant inhibition (P<0.001) of the insulinotropic effects of 10 mM 2-ketoisocaproic acid (KIC) and 10 mM alanine were observed. These data suggest that BTS 67 582 shares a common signalling pathway to sulphonylurea but not imidazoline drugs. Desensitization of drug action may provide an important approach to dissect sites of action of novel and established insulinotropic antidiabetic agents.

Animals↗
PubMed1999

Thiazolidinediones: a new class of antidiabetic drugs.

Thiazolidinediones (TZDs) are a new class of oral antidiabetic agents. They selectively enhance or partially mimic certain actions of insulin, causing a slowly generated antihyperglycaemic effect in Type 2 (noninsulin dependent) diabetic patients. This is often accompanied by a reduction in circulating concentrations of insulin, triglycerides and nonesterified fatty acids. TZDs act additively with other types of oral antidiabetic agents (suphonylureas, metformin and acarbose) and reduce the insulin dosage required in insulin-treated patients. The glucose-lowering effect of TZDs is attributed to increased peripheral glucose disposal and decreased hepatic glucose output. This is achieved substantively by the activation of a specific nuclear receptor - the peroxisome proliferator-activated receptor-gamma (PPARgamma), which increases transcription of certain insulin-sensitive genes. To date one TZD, troglitazone, has been introduced into clinical use (in Japan, USA and UK in 1997). This was suspended after 2 months in the UK pending further investigation of adverse effects on liver function. TZDs have been shown to improve insulin sensitivity in a range of insulin-resistant states including obesity, impaired glucose tolerance (IGT) and polycystic ovary syndrome (PCOS). In Type 2 diabetes, the TZDs offer a new type of oral therapy to reduce insulin resistance and assist glycaemic control.

Administration, Oral↗
PubMed2003

[The use of oral antidiabetic drugs in the treatment of polycystic ovary syndrome].

The polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age. It is a complex metabolic-endocrine disorder with severe long-term health consequences like type 2 diabetes. The increased risk for cardiovascular diseases in women with PCOS is due to diabetes, adipositas and dyslipidemia. Insulin resistance plays a key role in the pathophysiology of this syndrome. This makes the use of oral antidiabetic drugs most compelling. The majority of studies have shown amelioration of the typical symptoms like hyperandrogenism and cycle irregularities. Ovulation and pregnancy rates increased. Furthermore these drugs might be cardioprotective by improving insulin sensitivity and reduce the risk for type 2 diabetes. This article reviews the use of different oral antidiabetic drugs in the treatment of PCOS and their influence on fertility, the risk for type 2 diabetes and cardiovascular diseases.

Acarbose↗
PubMed1981

Antidiabetic action of somatostatin after oral glucose loading: due to suppression of glucagon and growth hormone or of intestinal carbohydrate absorption?

To elucidate the mechanism by which somatostatin lowers blood glucose concentration and insulin requirement following carbohydrate ingestion in insulin dependent diabetic patients (IDDM; n = 6), the amount of insulin required for the assimilation of a 50 g glucose load was determined by means of an automated glucose-controlled insulin infusion system with and without concomitant somatostatin infusion. During the 3 hour period following glucose loading plasma concentrations of glucagon and growth hormone were diminished by somatostatin, as were the rise in blood glucose and insulin requirement (4.0 +/- 1.2 U) when compared with the control study (11.3 +/- 1.5 U; p less than 0.01). With cessation of somatostatin blood glucose levels and insulin requirement rose during the following 2 hour observation period (7.5 +/- 1.2 U) but remained basal during the control study (0.7 +/- 0.6 U; p less than 0.0005). Thus the integrated amounts of insulin required for glucose hormone were temporarily suppressed by somatostatin. It is concluded that the diminished insulin requirement and delayed rise in blood glucose during somatostatin administration after an oral glucose load is not due to its "antidiabetic" action by suppressing glucagon and growth hormone release. Our findings favour inhibition of intestinal carbohydrate absorption as the determining cause for the "antidiabetic" action of somatostatin.

Adult↗