Insulinotropic and ß-cell protective action of cuminaldehyde, cuminol and an inhibitor isolated from Cuminum cyminum in streptozotocin-induced diabetic rats.

Cuminum cyminum, a commonly used spice, is known to have anti-diabetic action. The present study aims towards the isolation of bioactive components from C. cyminum and the evaluation of their insulin secretagogue potential with the probable mechanism and ß-cell protective action. The anti-diabetic activity was detected in the petroleum ether (pet ether) fraction of the C. cyminum distillate and studied through in vivo and in vitro experiments. Bioactive components were identified through GC-MS, Fourier transform infrared spectroscopy and NMR analysis. The isolated components were evaluated for their insulin secretagogue action using rat pancreatic islets. Further, the probable mechanism of stimulation of islets was evaluated through in vitro studies using diazoxide, nifedipine and 3-isobutyl-1-methylxanthine. ß-Cell protection was evaluated using the (1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan) (MTT) assay, the alkaline comet assay and nitrite production. The administration of the pet ether fraction for 45 d to streptozotocin-induced diabetic rats revealed an improved lipid profile. Cuminaldehyde and cuminol were identified as potent insulinotrophic components. Cuminaldehyde and cuminol (25 µg/ml) showed 3·34- and 3·85-fold increased insulin secretion, respectively, than the 11·8 mm-glucose control. The insulinotrophic action of both components was glucose-dependent and due to the closure of the ATP-sensitive K (K⁺-ATP) channel and the increase in intracellular Ca²âº concentration. An inhibitor of insulin secretion with potent ß-cell protective action was also isolated from the same pet ether fraction. In conclusion, C. cyminum was able to lower blood glucose without causing hypoglycaemia or ß-cell burn out. Hence, the commonly used spice, C. cyminum, has the potential to be used as a novel insulinotrophic therapy for prolonged treatment of diabetes.

Antidiabetic activity of Kalanchoe pinnata in streptozotocin-induced diabetic rats by glucose independent insulin secretagogue action.

CONTEXT: Kalanchoe pinnata Lam. (Crassulaceae) is used as a traditional medicine worldwide to treat several ailments, including diabetes. However, the mechanism for the antihyperglycemic action is unknown. OBJECTIVE: The present study evaluates the antihyperglycemic and insulin secretagogue potential of Kalanchoe pinnata and assessment of the probable mechanism of action. MATERIALS AND METHODS: Steam distillate of Kalanchoe pinnata leaves was subjected to solvent fractionation and antidiabetic activity was detected in dichloromethane (DCM) fraction. In the in vivo studies, rats were treated with 5 and 10 mg/kg body weight of DCM fraction for 45 days orally. Lipid profile and other biochemical parameters were estimated. The probable mechanism for insulin secretagogue action was evaluated through studies using diazoxide and nifedipine. The bioactive component from DCM fraction was studied using HPTLC, GCMS and IR. RESULTS AND DISCUSSION: Fasting blood glucose values were reduced to 116 mg/dl from 228 mg/dl on treatment with 10 mg/kg body weight of DCM fraction, while glycated hemoglobin improved to 8.4% compared with 12.9% in diabetic controls. The insulin level and lipid profile values were close to normal values. In vitro studies demonstrated a dose-dependent insulin secretagogue action. Insulin secretion was 3.29-fold higher at 10 µg/ml as compared to the positive control. The insulin secretagogue activity was glucose independent and K(+)-ATP channel dependent. The bioactive component of the DCM fraction was identified to be a phenyl alkyl ether derivative. CONCLUSION: The DCM fraction of Kalanchoe pinnata demonstrates excellent insulin secretagogue action and can be useful in treatment of diabetes mellitus.

Squash Cytology Diagnosing Plasmacytoma of Frontal Bone as First Presentation of Nonsecretory Multiple Myeloma.

Plasmacytoma of bone is one of the criteria for diagnosing plasma cell myeloma (multiple myeloma). A plasmacytoma involving a frontal bone is unusual, with only few being reported so far. Also, when typical clinical presentation is absent, diagnosis is usually not suspected clinicoradiologically. We report a rare case of frontal bone plasmacytoma presenting as a lump over the forehead, the squash cytology of which gave the diagnosis of neoplastic etiology. Thus, squash cytology helped in early and definitive diagnosis in this patient, hastening meticulous diagnostic investigations and appropriate management. With full workup, the final diagnosis of a nonsecretory multiple myeloma was made.

Antihyperglycemic and antihyperlipidemic effect of Santalum album in streptozotocin induced diabetic rats.

CONTEXT: Santalum album Linn (Santalaceae), commonly known as Sandalwood is used traditionally for its antihyperlipidemic and diuretic activity. OBJECTIVE: This study investigated the antihyperglycemic and antihyperlipidemic effect of long-term oral administration of the Santalum album pet ether fraction in streptozotocin-induced diabetic rats. MATERIALS AND METHODS: Diabetes was induced by a single intraperitoneal injection of streptozotocin at 70 mg/kg body weight. Rats were treated with Santalum album pet ether fraction orally at a dose of 10 µg/kg body weight twice daily for 60 days. Metformin (30 mg/kg body weight) was used as positive control. Lipid profile and glycated hemoglobin were estimated. HPLC profiling of Santalum album pet ether fraction was carried out. RESULTS AND DISCUSSION: Treatment of diabetic rats for 60 days demonstrated reduction in blood glucose level by 140 mg/dl. Metformin treated group showed a decrease in blood glucose by 70 mg/dl, as against an increase in diabetic control group by 125 mg/dl. Total cholesterol (TC), low density lipoprotein (LDL) and triglyceride (TG) levels were decreased by 22, 31 and 44%, respectively, in treated diabetic rats whereas, cardioprotective, high density lipoprotein (HDL) increased by 46%. In case of metformin, the values were 11, 29 and 15% respectively, while HDL increased by 7%. Significant improvement in atherogenic index from 267 to 139% was observed in treated rats. CONCLUSION: Santalum album pet ether fraction has potential antihyperlipidemic activity that can help in overcoming insulin resistance.

Mesenchymal stem cell-based treatment for microvascular and secondary complications of diabetes mellitus.

The worldwide increase in the prevalence of Diabetes mellitus (DM) has highlighted the need for increased research efforts into treatment options for both the disease itself and its associated complications. In recent years, mesenchymal stromal cells (MSCs) have been highlighted as a new emerging regenerative therapy due to their multipotency but also due to their paracrine secretion of angiogenic factors, cytokines, and immunomodulatory substances. This review focuses on the potential use of MSCs as a regenerative medicine in microvascular and secondary complications of DM and will discuss the challenges and future prospects of MSCs as a regenerative therapy in this field. MSCs are believed to have an important role in tissue repair. Evidence in recent years has demonstrated that MSCs have potent immunomodulatory functions resulting in active suppression of various components of the host immune response. MSCs may also have glucose lowering properties providing another attractive and unique feature of this therapeutic approach. Through a combination of the above characteristics, MSCs have been shown to exert beneficial effects in pre-clinical models of diabetic complications prompting initial clinical studies in diabetic wound healing and nephropathy. Challenges that remain in the clinical translation of MSC therapy include issues of MSC heterogeneity, optimal mode of cell delivery, homing of these cells to tissues of interest with high efficiency, clinically meaningful engraftment, and challenges with cell manufacture. An issue of added importance is whether an autologous or allogeneic approach will be used. In summary, MSC administration has significant potential in the treatment of diabetic microvascular and secondary complications but challenges remain in terms of engraftment, persistence, tissue targeting, and cell manufacture.