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Introduction: More than 424 million adults have diabetes mellitus (DM). This number is expected to increase to 626 million by 2045. The majority (90-95%) of people with DM has type 2-diabetes (T2DM). The continued prevalence of DM and associated complications has prompted investigators to find new therapies. One of the most recent additions to the anti-diabetic armamentarium are inhibitors of sodium-glucose co-transporters 1 and 2 (SGLT1, SGLT2). Areas covered: The authors review the status of SGLT2 inhibitors for the treatment of T2DM and place an emphasis on those agents in early phase clinical trials. Data and information were retrieved from American Diabetes Association, Diabetes UK, ClinicalTrials.gov, PubMed, and Scopus websites. The keywords used in the search were T2DM, SGLT1, SGLT2, and clinical trials. Expert opinion: The benefits of SGLT inhibitors include reductions in serum glycated hemoglobin (HbA1c), body weight, blood pressure and cardiovascular and renal events. However, SGLT inhibitors increase the risk of genitourinary tract infections, diabetic ketoacidosis, and bone fractures. The development of SGLT inhibitors with fewer side effects and as combination therapies are the key to maximizing the therapeutic effects of this important class of anti-diabetic drug.

The number of people with diabetes mellitus (DM) is estimated to exceed 640 million by the year 2040. Diabetic foot ulcer (DFU) is a debilitating illness that affects more than 2% of DM patients. DFU is caused by DM-induced neural and vascular lesions leading to a reduced sensation and microcirculation. The increase in the prevalence of DFU has prompted researchers to find new therapies for the management of DFU. Areas covered: This review presents the current status of novel biological therapies used in the treatment of DFU. Literature information and data analysis were collected from PubMed, the website of the American Diabetes Association, and ClinicalTrials.gov. The keywords used in the search were: DM, DFU, complications of DM. Expert opinion: Many biological agents have been investigated in a bid to find an effective therapy for DFU. These include growth factors (platelet-derived growth factor, vascular endothelial growth factor etc), stem cells (epithelial progenitor-, adipose-derived stem cells etc), anti-diabetic drugs (insulin, exendin-4), herbs, urokinase, dalteparin, statins and bio-agents such as acid peptide matrix. Biological agents that can reduce hyperglycaemia, increase sensation, microcirculation and oxygenation and repair lost tissue are the most ideal for the treatment of DFU.

Hypoxia injury (HI) with its long-term neurological complications is one of the leading causes of morbidity and mortality in the world. Currently, the treatment regimens for hypoxia are aimed only at ameliorating the damage without complete cure. The need, therefore, for novel therapeutic drugs to treat HI continues.This study investigates the protective effects of the ethanol extract of Cyperus rotundus L. (Cyperaceae) (EECR), a medicinal plant used in Ayurvedic traditional medicine against sodium nitrite-induced hypoxia in rats.We have evaluated the protective effect of 200 and 400 mg/kg of EECR against sodium nitrite-induced hypoxia injury in rats by assessing the cognitive functions, motor, and behavioral effects of EECR treatment along with the histological changes in the brain. By comparing the protective effects of standard drugs galantamine, a reversible cholinesterase inhibitor and pyritinol, an antioxidant nootropic drug against sodium nitrite-induced hypoxia in rats, we have tested the protective ability of EECR.EECR at doses of 200 and 400 mg/kg was able to protect against the cognitive impairments, and the locomotor activity and muscular coordination defects, which are affected by sodium nitrite-induced hypoxia injury in rats.Based on our results, we suggest that the medicinal herb C. rotundus possesses a protective effect against sodium nitrite-induced hypoxia in rats. Further studies on these protective effects of EECR may help in designing better therapeutic regimes for hypoxia injury.

The pattern of distribution of resistin in the pancreas of diabetic patients was investigated to determine whether diabetes mellitus influences the expression of resistin. Pancreatic tissue samples retrieved, during pancreatectomy for pancreatic cancer, from cancer patients with and without type 2 diabetes were processed for immunohistochemistry. The pancreatic tissue samples were retrieved from non-cancerous and clear margins. An immunofluorescence technique was used to examine the expression of resistin and its co-localization with insulin and glucagon in pancreatic islet cells. Resistin was observed in many cells located in the central region of pancreatic islet. The expression of resistin increased significantly (p < 0.0001) in pancreatic islet cells of type 2 diabetic patients compared to control. Resistin co-localized with insulin but not glucagon in pancreatic islet cells of both normal and diabetic patients. However, the degree of co-localization was higher in pancreata of diabetic patients compared to normal. The number of human pancreatic islet cells expressing resistin increased significantly after the onset of type 2 diabetes. In conclusion, resistin may play a role in the regulation of pancreatic β-cell function.

Vasoactive intestinal polypeptide (VIP) is an inhibitory non-adrenergic, non-cholinergic transmitter, which mediate in the relaxation of sphincters of the gastrointestinal tract. The aim of this study was to determine whether there is a change in the pattern of innervation and tissue content of VIP in the rat gastroduodenum after the onset of streptozotocin (STZ)-induced diabetes mellitus. Diabetes was induced by a single intraperitoneal injection of STZ (60 mg Kg(-1)). Four weeks after the induction of diabetes mellitus, the rats were anaethetised and the pancreata were removed for further processing. VIP was localized and measured in normal and diabetic rat gastroduodenal tissues by immunohistochemistry and radioimmunoassay, respectively. VIP immunoreactivity was stronger in the ganglion cells of the submucosal and myenteric plexuses of the gastric antrum and duodenum of normal rats (n = 6) when compared to that of diabetic rats (n = 6). Moreover, the number of VIP-positive neurons was significantly lower in the gastrointestinal tract of diabetic rats compared to normal. The VIP content of the gastric antrum and duodenum of diabetic rat was significantly lower (p0.05) than that of normal rat. In contrast to the lower tissue levels of VIP in the gastroduodenal segment of diabetic rats, the plasma level of VIP was significantly higher (p0.04) in diabetic rat compared to normal. The plasma level of VIP in normal rats was comparable to that measured in normal human beings. A low tissue level of VIP in the gastroduodenal tract of diabetic rat may contribute in part to the abnormal gut motility observed in diabetic patients.

The aim of this study was to examine the disease characteristics and complications of diabetes mellitus in patients in a Hungarian rural community. Data relating to age, sex, date of onset of diabetes, fasting blood glucose values and all diseases associated with diabetics were retrieved from the medical records of patients. Almost six percent (5.7%) of the population has diabetes mellitus. The percentage of Type I diabetic patients in this population was 5.8 percent. The prevalence of diabetes was slightly but not significantly higher in females than in males. The mean age of the diabetic population was 52.1 +/- 11.3 for male and 53.47 +/- 15.7 for the female patients. The peak age of onset of diabetes mellitus was in the sixth decade of life. The mean fasting blood sugar value was 10.64 +/- 0.6 and 10.57 +/- 0.5 mmol L(-1), in male and female diabetic patients (n = 103), respectively. Diabetic patients presented with many signs and symptoms in the general practice setting. The findings of this study showed that diabetics present with many disease conditions and signs and symptoms in the general practice setting. Many of these conditions are known to be associated with diabetes while others are not. As a result of the adverse effects of diabetes mellitus on the cardiovascular system and on body metabolism as a whole, the damage and morbidity caused by diabetes mellitus may have been underestimated. The results of this study have shed light on the unrecognised complications of diabetes mellitus.

Leucine-enkephalin (Leu-Enk) has been shown to be present in endocrine cells of the rat pancreas and may play a role in the modulation of hormone secretion from the islets of Langerhans. Since little is known about the effect of Leu-Enk on insulin and glucagon secretion, it was the aim of this study to determine the role of Leu-Enk on insulin and glucagon secretion from the isolated pancreatic tissue fragments of normal and diabetic rats. Pancreatic tissue fragments of normal and streptozotocin-induced diabetic rats were incubated for 1 h with different concentrations of Leu-Enk (10(-12)-10(-6)M) alone or in combination with either atropine or yohimbine or naloxone. After the incubation period the supernatant was assayed for insulin and glucagon using radioimmunoassay techniques. Leu-Enk (10(-12 )-10(-6)M) evoked large and significant increases in insulin secretion from the pancreas of normal rats. This Leu-Enk-evoked insulin release was significantly (p < 0.05) blocked by atropine, naloxone and yohimbine (all at 10(-6)M). In the same way, Leu-Enk at concentrations of 10(-12)M and 10(-9)M induced significant (p < 0.05) increases in glucagon release from the pancreas of normal rats. Atropine, yohimbine but not naloxone significantly (p < 0.05) inhibited Leu-Enk-evoked glucagon release from normal rat pancreas. In contrast, Leu-Enk failed to significantly stimulate insulin and glucagon secretion from the pancreas of diabetic rats. In conclusion, Leu-Enk stimulates insulin and glucagon secretion from the pancreas of normal rat through the cholinergic, alpha-2 adrenergic and opioid receptor pathways.

(2001). Diabetes Mellitus – Multifactorial in Aetiology and Global in Prevalence. Archives of Physiology and Biochemistry: Vol. 109, No. 3, pp. 197-199.