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Allosteric activators of human glucokinase (GK) had revealed significant hypoglycemic effects for therapy of type-2 diabetes (T2D) in animal as well as human models. Some newer N-benzimidazol-2yl substituted benzamide analogues were prepared and assessed for activation of GK accompanied by molecular docking investigations for predicting the bonding interactions of these derivatives with the residues in allosteric site of GK protein. Amongst the derivatives synthesized, compounds 2 and 7 strongly increased catalytic action of GK (GK activation fold >2.0 in comparison to control) in vitro. The results of in-vitro testing were supported by the molecular docking investigations of these analogues with GK protein’s allosteric site residues (showed appreciable H-bond interactions with Arg63 residue of GK). Derivatives investigated in present study afforded few lead compounds for the discovery of harmless and strong allosteric GK activating compounds for treating T2D.

Qingzhuan tea (QZT), a post-fermented tea, has been reported to have anti-obesity and anti-hyperglycemic effects, perhaps due to bioactive compounds that inhibit lipase and α-amylase. It is unknown what chemical constituents’ changes and what bioactive compounds occur during the manufacture of QZT. The aim of this study was to determine the secondary metabolites changes that occur during post-fermentation and how these changes affect the ability of QZT to inhibit the activities of lipase and α-amylase. During the processing steps, metabolites levels and their inhibitory effects on lipase and α-amylase were assessed. Changes in content and activities suggested that the first turn over or the second turn over was critical for the formation and conversion of bioactive compounds responsible for the anti-obesity and hypoglycemic effects. The relationship between constituents and activities was further evaluated by correlation analysis, which showed that amino acids and flavonoids might be responsible for the anti-obesity and anti-hyperglycemic effects of QZT. This study clarified that compounds were altered during pile fermentation of QZT and tentatively identified the bioactive compounds formed during QZT manufacture.

Thiazolo[2, 3-f]purine derivatives and their analogs – dihydrothiazolo[2, 3-f]purine, 7-(thietan-3-yl)purine, and 8-(2-hydroxypropylthio)purine derivatives – were synthesized. The compounds synthesized here had no effects on protein glycation reactions using glucose; they gave weak inhibition of glycogen phosphorylase; they had no hemorheological activity. Substances with hypotensive activity greater than that of Dibazol were found. A number of substances had hypoglycemic effects greater than those of chlorpropamide and Adebit. Two compounds inhibited dipeptidylpeptidase-4, but were less active than reference agent vildagliptin.

Background Berberine is one of the most important examples of a Chinese traditional medicine that has hypoglycemic effects but there have been no randomized controlled trials of the drug in a larger sample. In addition, the use of probiotic biotherapy to maintain an appropriate intestinal flora may represent an effective early intervention for hyperglycemia. Unfortunately, there has been a shortage of relevant research on this possibility at the population level. This study was designed to determine the hypoglycemic effect and safety of both bifidobacteria and berberine administration to newly diagnosed patients with pre-diabetes or diabetes mellitus. Methods/design This is a multicenter, double-blind, randomized, and parallel-controlled study that includes a run-in period of 2 weeks and a treatment period of 16 weeks, which will be conducted between June 2015 and October 2018. The 300 randomized patients will be assigned to the following four groups for 16 weeks’ treatment: Bifidobacterium, berberine, Bifidobacterium combined berberine, and placebo control groups. The primary outcome is the absolute value of fasting plasma glucose compared with baseline after 16 weeks of treatment. Discussion This is the first randomized controlled trial to determine the hypoglycemic effect and safety of both bifidobacteria and berberine administration to newly diagnosed patients with pre-diabetes or diabetes mellitus. It may provide support for the use of berberine and bifidobacteria in the treatment of diabetes. Trial registration ClinicalTrials.gov, ID: NCT03330184. Retrospectively registered on 18 October 2017. Electronic supplementary material The online version of this article (doi:10.1186/s13063-018-2438-5) contains supplementary material, which is available to authorized users.

A series of amides of 2,3-dihydroimidazo- and 2,3,4,10-tetrahydropyrimido[1,2-a]benzimidazolyl-N-acetic acids were synthesized. Their pharmacological activity was studied. It was established that the synthesized substances possessed antiaggregant properties and antiarrhythmic activity. Some of these amides exhibited antioxidant and hypoglycemic effects in addition to antagonist activity with respect to serotonin 5-HT2 and purine P2Y1 receptors.

Two kinds of insulin were loaded into self-dissolving micropile array tip (following tip). Fully-loaded tip (f-tip) and partially-loaded tip (p-tip) were prepared using chondroitin sulfate for the percutaneous administration of insulin. One hundred micropiles were constructed on a 1.0 x 1.0 cm tip. The mean length of the micropile in a tip were 483.4 +/- 4.7 mum for the f-tip and 492.6 +/- 2.4 mum for the p-tip. The insulin content of the p-tip was 28.5% of that of the f-tip. The pharmacological efficiency of insulin loaded tip was evaluated in rat experiments by measuring their hypoglycemic effects. The maximum hypoglycemic effect of insulin was observed at 1.7 +/- 0.2 h for the f-tip and 1.5 +/- 0.2 h for the p-tip. Good dose-dependency was observed for the plasma glucose level vs. time curves. These results suggest the usefulness of p-tip as a percutaneous DDS of insulin.

The novel gluconeogenesis inhibitor FR225654, isolated from the culture broth of Phoma sp. No. 00144, has an unique structure that consists of a highly oxygenated trans-decalin ring and a beta-keto-enol, with a characteristic side chain. This compound selectively inhibited gluconeogenesis of rat primary hepatocytes and had hypoglycemic effects in several in vivo mouse models.

Previously, we have synthesized alkyl(aryl)amides of 2-chloro-, 2-amino-, and 2-arylaminonicotinic acids possessing anticonvulsant activity [1, 2]; 2-chloro-, 2-methoxy-, and 2-hydroxynicitinic acid amides, some of which exhibited antiinflammatory activity [3, 4]; and 2-arylhydroxynicotinonitriles and unsubstituted amides of 2-arylhydroxynicotinic acids producing antiinflammatory and hypoglycemic effects [5]. In the search for new antiinflammatory and antibacterial agents in the group of 2-substituted nicotinic acid amides, we have synthesized a series of nicotinamides containing pharmacophore 4-sulfamylanilino or aryloxy groups at C-2 atom of the pyridine ring.

People in some tropical countries used to use some plant extracts in folklore medicine as treatment of diabetes mellitus. Of these plants isCalligonum comsum (“orta”). The present work deals with the biochemical effects of the whole plant water extract given orally to the albino rats, normals and alloxan diabetics, as to fulfil its hypoglycemic effects on rats. The results showed that “orta” extract produced a hypoglycemic effect indicated by the decrease in blood sugar level. It was observed that the diabetic state in rats treated with 300 mg/kg body weight of “orta” extract, was alleviated, showing normal levels of blood glucose, liver fat and cholesterol contents. Liver proteins were still below the normal level in the rats. Gibenclamide, a hypoglycemic drug, was used for comparison with “orta” extract. Although it did alleviate the diabetic state, yet the liver fat and cholesterol contents were still higher than those of normal. Also the liver proteins were lower than the control levels.

E. creticum has been used in folk medicine in Jordan as a remedy for scorpion stings in the rural areas and as a hypoglycemic agent. The hypoglycemic activity of an aquous decoction of plant arial parts ofE. creticum was tested in normoglycemic and streptozocin-hyperglycemic rats. Results indicate that those extract caused significant reductions in blood glucose concentration when given orally.

Japanese researchers have uncovered a second mechanism by which sulfonylureas stimulate insulin production but avoid their hypoglycemic effects. One question is whether analogs targeting the mechanism could generate better results than marketed incretin analogs that work upstream.