Glucose Intolerance and Hyperlipidemia Prior to Diabetes Onset in Female Spontaneously Diabetic Torii (SDT) Rats

The Spontaneously Diabetic Torii (SDT) rat, a newly established animal model for diabetes mellitus, presents nonobese type 2 diabetes with ocular complications. In the present study, oral glucose tolerance tests and biochemical and histopathological examinations were performed in female SDT rats at 16 and/or 25 weeks of age, before the onset of diabetes. At 25 weeks of age, glucose tolerance was significantly impaired, and plasma immunoreactive insulin levels at 120 min after glucose loading were significantly higher (P< 0.05). Body weight and fasting levels of plasma triglycerides and nonesterified fatty acids were significantly higher than those in control animals. Histopathologically, inflammatory cell infiltration and fibrosis were observed in and around the pancreatic islets. These results strongly suggest that female SDT rats are useful as a model to investigate impairment of glucose tolerance and hyperlipidemia prior to the onset of diabetes.

Correlation between the urinary excretion of acid-soluble peptides, fractional synthesis rate of whole body proteins, and plasma immunoreactive insulin-like growth factor-l/somatomedin C concentration in the rat

The relations between the urinary excretion of acid-soluble peptide (ASP)-form amino acids, the rate of whole body protein synthesis and plasma immunoreactive insulin-like growth factor-1/somatomedin C concentration were investigated in rats. The urinary ASP-form leucine plus valine excretion correlated well with the rate of whole body protein synthesis and with the plasma immunoreactive insulin-like growth factor-1 concentration. The results provide further evidence for the hypothesis that urinary excretion of ASP is an excellent index of the status of protein metabolism in animals.

Attenuation of streptozotocin-induced diabetes in rats by pretreatment with chloroquine

1. The effect of chronic administration of chloroquine on glucose homoeostasis was investigated in normal and diabetic rats by determining fasting plasma glucose, glycated plasma protein, plasma immunoreactive insulin, plasma protein and glycated haemoglobin. Animal weights, as well as the survival of the diabetic animals without insulin therapy, were also observed. 2. Apart from an elevation in the plasma immunoreactive insulin levels (4.1 ± 0.6 vs 2.1 ± 0.4 μg/l, P < 0.025), there were no significant differences among the other parameters compared with age-matched controls up to week 12 for the normal rats on chloroquine treatment. After 20 weeks of treatment, however, plasma glucose (7.2 ± 0.1 vs 8.4 ± 0.2 mmol/l, P < 0.005) and glycated haemoglobin (2.9 ± 0.1 vs 3.3 ± 0.1%, P < 0.01) levels were lower in the treated animals. Diabetic rats treated with chloroquine for 12 weeks before the onset of diabetes showed significantly higher plasma insulin and protein levels than control diabetic animals, while plasma glucose (17.7 ± 2.5 vs 29.4 ± 1.7 mmol/l, P < 0.005), glycated plasma protein and glycated haemoglobin (6.6 ± 0.4 vs 7.8 ± 0.4%, P < 0.05) levels were lower. 3. It is concluded that after a prolonged administration of chloroquine there is a hypoglycaemic effect in normal animals, and pretreatment with the drug ameliorates diabetes induced subsequently.

Preventive action of phentolamine on adrenaline induced blood glucose elevation in humans

A comparison of the action of adrenaline infusion and a combined adrenaline + alpha blocker (phentolamine, Regitine®) infusion on blood glucose (BG), plasma immunoreactive insulin (IRI), BG/IRI ratio, C-peptide, and plasma cortisol levels was made in healthy young human subjects. The purpose of the experiment was to check, whether alpha block could abolish adrenaline-induced enhancement of blood glucose levels. The results show that during enhanced adrenaline levels, the use of regitine could indeed normalize blood glucose levels, not so much by increasing the IRI secretion, but by diminishing adrenalineinduced liver glycogenolysis via alpha receptors. This could be a model to prevent stress (adrenaline) induced metabolic deviations in diabetics, especially before and during predictable stress situations, e.g. examinations or surgery.

Effect of fasting interval on CCK-8 suppression of food intake in the baboon

Baboons were infused intravenously for 5 min with the octapeptide of cholecystokinin (CCK-8) after either a 16.5- or 3.5-h fast. After a 3.5-h fast, food intake was significantly suppressed over the ensuing 30 min by 2 micrograms/kg of CCK-8 (-156 +/- 34 kcal compared with control days, P less than 0.02) and by 4 micrograms/kg of CCK-8 (-257 +/- 31 kcal, P less than 0.01). In contrast, CCK-8 had no reliable effect on food intake after the same baboons had been fasted for 16.5 h (2 micrograms/kg: -93 +/- 40 kcal, P greater than 0.05; 4 micrograms/kg: -30 +/- 82 kcal, P greater than 0.05). There was no reliable effect of 1 microgram/kg of CCK-8 on food intake at either deprivation interval. CCK-8 infusions resulted in a small increase of fasting plasma immunoreactive insulin (IRI); this effect was not related to either dose or deprivation length. Postprandial IRI and glucose concentrations were significantly suppressed by CCK-8 independently of its effect on food intake. Thus, after a 16.5-h fast, 4 micrograms/kg of CCK-8 decreased postprandial IRI from 145 +/- 65 to 29 +/- 4 microU/ml (P less than 0.01) and glucose from 101 +/- 5 to 80 +/- 3 mg/dl (P less than 0.02), despite no concomitant effect on food intake. Similar suppression of plasma IRI and glucose were observed after infusions of 1 and 2 micrograms/kg in 16.5-h-fasted animals. All doses of CCK-8 (1, 2, and 4 micrograms/kg) suppressed postprandial IRI and glucose after a 3.5-h fast.(ABSTRACT TRUNCATED AT 250 WORDS)