Amelioration of diabetic nephropathy by SGLT2 inhibitors independent of its glucose-lowering effect: A possible role of SGLT2 in mesangial cells.

Several clinical studies have shown the beneficial effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on diabetic nephropathy. The underlying mechanisms are not fully understood. We found that administration of canagliflozin at a low dose (0.01 mg/kg/day) did not affect either blood glucose levels or glycosuria, but it improved albuminuria and mesangial expansion in db/db mice to a similar extent as at a high dose (3.0 mg/kg/day) that lowered blood glucose levels. This indicated the existence of a tubular SGLT2-independent reno-protective mechanism. Here we focused on the potential role of SGLT2 in mesangial cells (MCs). Western blot analysis revealed the expression of SGLT2 in cultured mouse MCs. Exposure of MCs to high glucose levels for 72 h significantly increased the expression of SGLT2. Canagliflozin or ipragliflozin (both 100 nM) treatment inhibited glucose consumption in the medium under high-glucose conditions but not under normal-glucose conditions. Furthermore, canagliflozin inhibited high-glucose-induced activation of the protein kinase C (PKC)-NAD(P)H oxidase pathway and increases in reactive oxygen species (ROS) production. Thus, the inhibition of mesangial SGLT2 may cause an inhibition of PKC activation and ROS overproduction in diabetic nephropathy, and this may at least in part account for the reno-protective effect of SGLT2 inhibitors.

Antidiabetic and antioxidant potential of ß-sitosterol in streptozotocin-induced experimental hyperglycemia.

BACKGROUND: Oxidative stress, produced under diabetic conditions, may cause tissue damage. Although several drugs are currently available for the treatment of diabetes, their continued use may cause unwanted side effects. The aim of the present study was to evaluate the antioxidant potential of ß-sitosterol (BS), a phytosterol from Solanum surattense, using an experimental model for diabetes-induced oxidative damage. METHODS: The effects of 21 days treatment with BS (10, 15 and 20 mg/kg, p.o.) on blood, serum, and tissue biochemical parameters were evaluated in control and streptozotocin-induced diabetic rats. Nine experimental groups, including a control group, a diabetic group, and BS- and glibenclamide-treated diabetic groups, were evaluated. RESULTS: All three dose levels dose dependently resulted in decreases in glycated hemoglobin, serum glucose, and nitric oxide, with concomitant increases in serum insulin levels. Furthermore, treatment with BS doses also increased pancreatic antioxidant levels, with a concomitant decrease in thiobarbituric acid-reactive substances. CONCLUSIONS: ß-Sitosterol has promising antidiabetic as well as antioxidant effects and may be considered in clinical studies for drug development.

[The influence of peloids from volcanic deposits in Azerbaijan on the dynamics of sugar content in blood and urine and the wound healing in patients at the early stages of diabetic gangrene of the lower extremities].

The treatment of diabetic patients with pyonecrotic lesions in the lower extremities requires prolonged reflexo-segmental balneophysiotherapy to normalize functions of the nerve centres. Curative volcanic mud solutions (15-24 g/l) enriched with organic and nonorganic biologically active compounds from volcanic deposits in Azerbaijan were used for the first time to treat such patients. Peloids were applied to the lumbar region (location of sympathetic nerve nodes) and the lower legs above and beneath the affected sites. The patients were subjected to 12-15 seances of peloidotherapy (at 40-41 degrees Celsius) each lasting 20-30 minutes. The treatment was preceded by wound sanation using the standard procedure and a course of antibiotic therapy based on individual antibiotocograms. A total of 86 daibetic patients with leg gangrene underwent rheovasographic thermovision examination that revealed enhanced blood supply to the affected extremities under the action of the applied peloids. Peloidotherapy resulted in the normalization of blood and urine glucose levels in 53 (63%) of the patients. Simultaneously, the doses of medicamentous therapy could be lowered. Wound and ulcer healing was completed in the majority of the patients (86%) by the end of balneophysiotherapy when fresh granulation tissue began to develop and signs of oedema to disappear. These patients no longer needed amputation.

[The use of homeopathy in treating diabetics]. / Primenenie gomeopatii v lechenii bol'nykh sakharnym diabetom.

The rationale of homeopathic treatment of diabetes mellitus (DM) with constitutional predisposition is discussed. On the basis of a detailed analysis of one case the author describes the method of homeopathic treatment of diabetes mellitus. The treatment is orientated not only on the treatment of DM but also of concomitant diseases with emphasis in the patients constitution. Minimal doses of homeopathic treatment used in 68 patients resulted in a statistically valid stable reduction of hyperglycemia and glucosuria. Stable subcompensation and compensation of DM allowed to decrease the dose of sugar reducing drugs.