M A Ghatei — Page 21 | PubMed Health

PubMedDate not supplied

Increased hypothalamic neuropeptide Y messenger RNA levels in two rat models of diabetes.

Elevated levels of immunoreactive hypothalamic neuropeptide Y have recently been reported both in streptozotocin-induced diabetic rats and in the spontaneously diabetic BB rat. We have measured the levels of neuropeptide Y encoding messenger ribonucleic acid (mRNA) in both of these rat models to determine whether an increase in neuropeptide Y gene expression is a contributory factor to the increases in hypothalamic neuropeptide Y immunoreactive peptide content. In the hypothalami of both the spontaneously diabetic BB/E and the streptozotocin-diabetic animals, neuropeptide Y mRNA showed significant elevations (to 204 +/- 13% (+/- SE) and 387 +/- 48% of control values, respectively, p less than 0.01 for both). Our results demonstrate that two models of insulin-deficient diabetes in the rat are associated with increased hypothalamic neuropeptide Y mRNA. Taken with the known effects of neuropeptide Y on food intake these results suggest that increased neuropeptide Y synthesis in the hypothalamus may be related to the hyperphagia seen in the diabetic condition.

Animals↗

PubMedDate not supplied

Effect of the aldose reductase inhibitor, ponalrestat, on diabetic neuropathy.

The effect of treatment with the aldose reductase inhibitor, Ponalrestat*, was studied in 30 diabetic patients with established peripheral and autonomic neuropathy. After a 4-week placebo run-in phase, patients were randomised to 16 weeks active or placebo treatment in a double-blind, parallel-group trial. Changes in neuropathy were assessed using vibration perception thresholds, heart rate responses to deep breathing, pulse and blood pressure changes on standing and the patients' subjective scoring of peripheral and autonomic neuropathic symptoms. In addition, circulating neuropeptides and the responses of circulating gut peptides to an oral glucose tolerance test were studied. There was a significant improvement in the mean vibration perception threshold over the four sites studied in the ponalrestat treated group. There were no significant changes in the other indices of neuropathy, including heart rate variability, blood pressure responses to standing or symptom scores, though there were trends towards improvement. There were no significant changes in the levels of the circulating neuropeptides or in the responses of the circulating gut peptides to oral glucose tolerance test. No clinically important side-effects attributable to ponalrestat were observed. We conclude that ponalrestat improves some of the parameters of diabetic neuropathy and is likely to be of value in the treatment of this condition.

Adult↗