Modulation of glucose uptake in adipose tissue by nitric oxide-generating compounds.

There is increasing evidence that endogenous nitric oxide (NO) influences adipogenesis, lipolysis and insulin-stimulated glucose uptake. We investigated the effect of NO released from S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP) on basal and insulin-stimulated glucose uptake in adipocytes of normoglycaemic and streptozotocin (STZ)-induced diabetic rats. GSNO and SNAP at 0.2,0.5, and 1 mM brought about a concentration-dependent increase in basal and insulin-stimulated 2-deoxyglucose uptake in adipocytes of normoglycaemic and STZ-induced diabetic rats. SNAP at 1.0 mM significantly elevated basal 2-deoxyglucose uptake (115.8+/-10.4% compared with GSNO at the same concentration (116.1+/-9.4%; P less than 0.05) in STZ-induced diabetic rats. Conversely, SNAP at concentrations of 10 mM and 20 mM significantly decreased basal 2-deoxyglucose uptake by 50.0+/-4.5% and 61.5+/-7.2% respectively in adipocytes of STZ-induced diabetic rats (P less than 0.05). GSNO at concentrations of 10 mM and 20 mM also significantly decreased basal 2-deoxyglucose uptake by 50.8+/-6.4% and 55.2+/-7.8% respectively in adipocytes of STZ-induced diabetic rats (P less than 0.05). These observations indicate that NO released from GSNO and SNAP at 1 mM or less stimulates basal and insulin-stimulated glucose uptake,and at concentrations of 10 mM and 20 mM inhibits basal glucose uptake. The additive effect of GSNO or SNAP, and insulin observed in this study could be due to different mechanisms and warrants further investigation.

Kidney function in phasic insulin dependent diabetes mellitus in Jamaica

In Jamaica, malnutrition related diabetes mellitus (MRDM) presents the clinical picture of phasic insulin dependence. This study was undertaken to investigate nephropathic changes associated with this group of patients. Fourteen phasic insulin dependentdiabetes mellitus (PIDDM) patients were compared with 10 insulin dependent (IDDM) and 10 non-insulin dependents (NIDDM) diabetes mellitus patients, and 10 normal controls. Each group was matched for age, sex, body mass index (BMI) and, in the case of the diabetic patient controls, duration of diabetes. Urinary microalbumin concentration was significantly (p < 0.05) higher in the PIDDM group (mean + SD: 153 + 48.3 mg/dl) than in the groups of NIDDM (35.7 + 9.6 mg/dl) or IDDM (38.6 + 15.8 mg/dl) patients. Serum urea and creatinine concentration (mean + SE 7.6 + 1.0 mmol/l and 130.0 +20.3 umol/l, respectively) were higher in the PIDDM patients than in the NIDDM and IDDM groups. Confounding factors such as hypertension and urinary tract infections were excluded as causes for these differences. We conclude that PIDDM patients have more severe renal dysfunction than NIDDM patients and, since glycosylated haemoglobin concentrations are comparable in these groups, we attribute this to a renal insult due to malnutrition predating the onset of PIDDM.

Clinical and biochemical features of malnutrition related diabetes mellitus

The aims of this study were to characterize clinically and biochemically malnutrition related diabetes mellitus (MRDM) as it presents in Jamaica (J-type or phasic insulin dependent diabetes mellitus) and to examine the food toxin (linamarin)/malnutrition hypothesis as a possible aetiological factor in the onset of MRDM. The study was broadly divided into two major areas: (i) Clinical or patient study and (ii) Animal model study. The patient population consisted of thirty-four, (23 females, 17 males) who attend the Diabetic Outpatient Clinic of the University Hospital of the West Indies. This group consisted of 14 phasic insulin dependent diabetes mellitus (PIDDM) (8 females, 6 males) 10 non-insulin dependent diabetes mellitus (IDDM), (6 females, 4 males). Ten (10) normal (4 females, 6 males) subjects also participated. The diabetic and normal subjects were matched for age, body mass index and duration of diabetes (among diabetics). Comparitive studies were performed on insulin receptor binding, hormonal profile, glucose tolerance, blood status, renal, hepatic and pancreatic function. The results show a significantly decreased white and red blood cell binding to insulin (P<0.05), extensive kidney damage (P<0.05) and increased pancreatic echogenicity in PIDDM. These findings support a separate identity of the latter syndrome from Types 1 and 11 diabetes mellitus. In the animal model study, the dogs (male and female) were maintained on a diet of cornmeal cooked with chicken, fortified with Purina laboratory chow and water ad libitum. Malnutrition was induced by restricting the diet to a very small quantity of cornmeal only for a period of 7-10 days. The recovered dogs were re-fed the normal diet with added milk and multi-vitamin supplement. Linamarin dosage of 20 mg per kg body weight induced abnormally high glucose levels, and in two cases the hyperglycaemia was sustained for several days. There was an associated decrease in binding of insulin to erythrocytes and mononuclear leucocytes, as well as prevailng hypoinsulinaemia in the limarin-induced hyperglycaemic conditions. This animal study presents a possible aetiological model for malnutrition related diabetes mellitus (Summary)