The results of prolonged action of GLP-1 on some metabolic parameters.

Glucagon-like peptide (GLP-1) is widely considered as a potential drug against diabetes mellitus and obesity. It strongly stimulates the pancreas to produce and release insulin, even a few minutes after meal consumption. Because of this action, GLP-1 has been called an "incretin hormone". Moreover, GLP-1 decreases the level of glucose in the blood, independently of insulin. An obstacle to clinical application is the very short half-time of GLP-1 degradation by dipeptidyl-peptidase IV in the blood. This research was aimed at tracing all possible changes evoked by long-term application of GLP-1 in rats and comparison of two methods of application: osmotic minipumps and daily injections. In the 13-day experiment, samples of blood, muscle and liver from 24 male Wistar rats were used. Analysis included glycogen, glucose, triglycerides, free fatty acids, cholesterol, triiodotyronin, thyroxin, insulin and glucagon concentrations. The results show a lack of significant differences between both methods of application. We suggest this may be evoked by adaptation of the organism to the prolonged action of GLP-1.

The activity of fine afferent nerve fibres of the rat knee joint and their modulation by inflammatory mediators.

BACKGROUND: The origin of joint pain involves the activation of terminals of slowly conducting C and A-delta afferent fibres. The aim of this study was to characterize the slowly conducting nerve fibres supplying the rat knee joint and to illustrate the usefulness of this model for objective studies of the pathophysiological aspects of articular nociception and pain. MATERIAL AND METHODS: Using an in vivo model, single afferent fibres innervating normal and inflamed knee joints were isolated and electrophysiologically characterized. Responses of these fibres were examined after local mechanical stimulation (von Frey hairs) and rotations consisting of inward and outward rotations of the knee joint within (non-noxious) and outside (noxious stimuli) its normal working range. The chemosensitivity of afferent fibres was tested by applying excitatory and sensitizing agents. RESULTS: The nerve fibres supplying the rat knee joint responded to mechanical and chemical stimuli (bradykinin, capsaicin). Bradykinin, substance P and prostaglandin E2 sensitized a considerable percentage of nerve fibres to mechanical stimuli. CONCLUSIONS: The rat knee joint is a useful model to study nociception and inflammatory processes in an objective way. It can also be successfully used to study aspects of pain modulation.