Occurrence of an insulin-like peptide in extracts of human nervous tissue.

Peripheral nerves of the cat such as the vagal and the sciatic nerves have been shown to contain a peptide with insulin-like properties. The aim of the present study was to investigate whether insulin-like immunoreactivity (ILI) can be demonstrated in human nervous tissue collected from autopsy material. Biopsies were taken in connection with autopsy from various peripheral nerves and their content of ILI was investigated. ILI in amounts up to about 12 ng g-1 was found in about 30% of all biopsies taken from peripheral nerves. The ILI coeluted with a bovine insulin standard in an HPLC system indicating that it corresponds to a peptide identical with or similar to pancreatic insulin. Autopsy specimens taken from the sciatic nerve of individuals with diabetes type II or from individuals without established diabetes contained similar amounts of ILI.

Breast feeding-induced effects on plasma gastrin and somatostatin levels and their correlation with milk yield in lactating females.

Maternal gastrin and somatostatin levels have been shown to be influenced during suckling in dogs and pigs. The present study was performed to investigate whether the levels of gastrin and somatostatin are influenced by breast feeding in lactating women. Repeated blood samples were drawn in connection with nursing in 15 females and plasma levels of gastrin and somatostatin were measured by radioimmunoassay. Gastrin levels rose significantly (P = 0.01) within two minutes after onset of suckling. Somatostatin levels either decreased or increased as an effect of breast feeding. The direction of the change was correlated to the pre-suckling somatostatin levels (P less than 0.01). The somatostatin level recorded 60 min after start of breast feeding was significantly lower than basal levels (P less than 0.01) indicating a long-term inhibitory effect on somatostatin secretion. The suckling-induced effect on somatostatin levels was correlated with the amount of milk ejected (Rs - 0.52, P less than 0.05). The mechanism by which suckling influences circulating gastrin and somatostatin levels is unknown, but we suggest that suckling leads to a reflex activation of the vagal nerves, which influence the release of these hormones from the stomach. The size of the gastrointestinal tract is increased during pregnancy and lactation, illustrating that the maternal digestive capacity is adapted to the high demand for energy intake occurring during lactation. We speculate that the suckling stimulus enhances gastric functions by influencing the release of gastrin and somatostatin, which stimulate and inhibit gastric functions and growth, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence on plasma levels of somatostatin, gastrin, glucagon, insulin and VIP-like immunoreactivity in peripheral venous blood of anaesthetized cats induced by low intensity afferent stimulation of the sciatic nerve.

The objective of the present study was to investigate whether gastrointestinal hormones can be released in response to low intensity afferent activation of the sciatic nerve. Experiments were performed on anaesthetized cats in which the sciatic nerve was stimulated electrically at 3 Hz, to V and 0.2 ms. Blood samples were collected in a peripheral vein and the plasma levels of somatostatin, gastrin, glucagon, insulin and VIP-like immunoreactivity (below referred to as somatostatin, gastrin, glucagon, insulin and VIP) were recorded by radioimmunoassay. Afferent stimulation of the sciatic nerve caused immediate (approximately 15 min long) changes of the levels of all the above mentioned peptides. Somatostatin, gastrin and glucagon levels rose significantly, whereas in the case of insulin and VIP a significant relationship between the effect of sciatic nerve stimulation and basal levels was established. Thus, insulin and VIP levels decreased when basal levels were high and increased when basal levels were low. The secretion of gastrointestinal and pancreatic hormones is in part regulated by the autonomic nervous system. It is suggested that afferent stimulation of the sciatic nerve causes a reflex activation of the vagal and/or the splanchnic nerves, which in turn affects the release rate of the above-mentioned hormones. In conclusion, these data show that the release of gastrointestinal hormones can be influenced by low intensity stimulation of the sciatic nerve. The physiological trigger of these responses may be touching of the skin.

Release of an insulin-like peptide from perfused extirpated cat legs in response to electrical stimulation of the sciatic and brachial nerves and to administration of ACh, bombesin, oxytocin and glibenclamide.

The vascular system of extirpated cat legs was perfused with Tyrode's solution and insulin-like immunoreactivity (ILI) levels were determined in the perfusate with radioimmunoassay. During unstimulated conditions perfusate levels of ILI were almost undetectable. However, in response to electrical stimulation of the sciatic or brachial nerves (within a wide range of stimuli 5-40 V, 2-20 Hz and 0.2-40 ms) 1-20 ng of ILI was recorded in the perfusate. Blockers of cholinergic and adrenergic transmissions added to the perfusate did not influence the output of the ILI induced by nerve stimulation. Furthermore, after administration of acetylcholine (ACh) (0.1 and 10 micrograms kg-1), oxytocin (0.5 and 5 IU kg-1), glibenclamide (25 and 100 micrograms kg-1) and bombesin (100 and 500 micrograms kg-1) to the cat leg preparation, ILI appeared in the perfusate in amounts similar to those induced by electrical stimulation of the nerves. When subjected to high-performance liquid chromatography (HPLC) the insulin-like peptide detected in the cat leg perfusate following nervous stimulation, or administration of oxytocin and glibenclamide, co-eluted with a bovine insulin standard. We have previously shown that some peripheral nerves of the cat, such as the sciatic, brachial and vagal nerves, contain an insulin-like peptide with HPLC characteristics similar to the bovine insulin standard. It is therefore possible that the insulin-like peptide released from the isolated cat leg preparation by the above-mentioned stimuli derives from this nervous pool of insulin. Alternatively, the insulin-like peptide emanates from the striatal muscles innervated by the sciatic and brachial nerves, since also muscles have been shown to contain an insulin-like peptide.

Occurrence of an insulin-like peptide in extracts of peripheral nerves of th cat and in extracts of human vagal nerves.

Biopsies from various peripheral nerves were collected from living cats. The biopsies were extracted with acid ethanol and the insulin-like immunoreactivity (ILI) content of the extracts determined with radioimmunoassay. The vagal, sciatic and radial nerves contained on the average 90, 3 and 28 ng of ILI per gram nerve tissue (wet weight), respectively. In the sympathetic trunc no ILI was found. In order to partly purify and characterize the nerve ILI extracts these were run on an HPLC system. the ILI coeluted with standard bovine insulin. The same amounts of ILI were found in the nerve extracts whether run on the HPLC system or not. It can be concluded that all of the immunoreactive material of the nerve extracts corresponds to insulin or to a peptide very similar to insulin. In two cats the radial and sciatic nerves were ligated for 24 h. Two to ten times more ILI occurred in biopsies taken proximal to the site of ligation than in those from corresponding distal biopsies, indicating that the insulin-like material is transported distally within the nerves. ILI was found in extracts from vagal nerves taken from 3 days old human autopsy material. Also this human ILI coeluted with the bovine insulin standard in the HPLC system.

The distribution of somatomedins in the nervous system of the cat and their release following neural stimulation.

Recent evidence suggests a regulatory role in the nervous system for somatomedins. The present study, using a somatomedin radioreceptorassay which primarily detects insulin-like growth factors 1 and 2, shows that somatomedins are widely distributed throughout the nervous system of the cat. Whilst somatomedins were present in all CNS regions, the highest concentration occurred in the hypothalamus followed by cerebral cortex. In the spinal cord, the dorsal roots contained twice the concentration found in the ventral roots. Activity was also present in the sympathetic ganglia, vagus nerve and sciatic nerves. Following electrical stimulation of the brachial and sciatic nerves somatomedins were released into perfusates from extirpated cut limbs. These findings suggest that somatomedins may be neuroregulatory hormones.

Plasma levels of somatostatin following a test meal in dogs. Initial atropine resistant vagally mediated decrease of somatostatin levels and increase of gastrin and insulin levels.

Plasma levels of somatostatin like immunoreactivity (SLI), below referred to as somatostatin levels, were measured in peripheral plasma of conscious dogs. Basal somatostatin levels averaged 49 +/- 10 pM. Somatostatin as well as gastrin and insulin plasma levels were measured before and after feeding with and without prior atropinization. During the first 10 min after feeding somatostatin levels fell from 49 +/- 10 to 23 +/- 9 pM, whereas gastrin and insulin levels rose from 9 +/- 2 and 140 +/- 14 pM to 48 +/- 11 and 370 +/- 91 pM respectively. Atropine 0.01 or 0.1 mg/kg did not inhibit these responses. After the initial decrease, somatostatin level rose again and peaked at around 60 min after feeding (110 +/- 24 pM). This secondary rise was completely abolished by atropine in both doses tried. Gastrin and insulin levels remained elevated throughout the experiments with and without atropine. It is suggested that gastrin release and HCl secretion are inhibited by a tonic outflow of gastric somatostatin during basal conditions. The process of feeding induces an atropine resistant, vagally mediated decrease in somatostatin release from the gastrointestinal tract and this decreased output of somatostatin facilitates initiation of meal-related endocrine and exocrine gastric secretions.