Thyrotropin-releasing hormone (TRH), but not histidyl-proline diketopiperazine (cyclo[His-Pro]), induced transient hyperglycemia associated with hyperglucagonemia and marked hyperinsulinemia when placed intracerebroventricularly (i.c.v.) in anesthetized rats. This TRH-induced hyperglycemia was prevented by acute adrenalectomy. However, adrenalectomy did not prevent TRH-induced hyperinsulinemia or hyperglucagonemia. In streptozotocin-induced diabetic rats, i.c.v. administration of TRH caused progressive and pronounced hyperglycemia. i.c.v. TRH-induced hyperinsulinemia was abolished by vagotomy and by systemic administration of hexamethonium or atropine. These results suggest that TRH induces hyperglycemia mediated by stimulation of the sympathetico-adrenal system and hyperinsulinemia by stimulation of the vagus nerve, and that the rapid decline of plasma glucose levels following transient hyperglycemia is due to hyperinsulinemia.

Abstract. The intracerebroventricular (icv) administration of 100 ng glucagon resulted in more prolonged and pronounced elevations of plasma glucose levels than the intravenous injection of 100 ng glucagon. Insignificant changes in plasma IRI and IRG levels after icv glucagon administration contrasted to marked increases in both IRI and IRG levels after the iv injection. Icv glucagon-induced hyperglycaemia was completely prevented by the prior administration of atropine, phentolamine or hexamethonium, and partially inhibited by bilateral adrenalectomy, but not by propranolol pretreatment. These findings suggested that the hyperglycaemic effect is brought about through cholinergic and α-adrenergic neural pathways and partly via the adrenal medulla.

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The effect of prolonged diabetic state on catecholamine-induced adenosine 3', 5'-monophosphate (CAMP) response in the rat liver was examined using isolated liver perfusion. Epinephrine-or isoproterenol-induced cAMP production was enhanced (10-fold of the control) in the liver from extremely emaciated (intraperitoneal adipose tissue was absent completely) diabetic rats 4 weeks after streptozotocin-injection kept without insulin, but not from adipose tissuepresent diabetic rats. Glucagon-induced cAMP production was decreased in the diabetic rat liver 4 weeks after streptozotocin regardless of the presence or absence of adipose tissue. Secretin-induced CAMP production was also decreased in the adipose tissue-absent diabetic rat liver. Plasma levels of glucose or insulin were not different between adipose tissue-present and -absent diabetic rats. Liver dysfunction (elevated AST and ALT levels) was observed 1 week after streptozotocin-injection, and worsened at 4 weeks. Forskolin-induced production of cAMP, and oxymetazoline (an «2-adrenergic agonist)-induced suppression of it were not different among the control, newly diabetic (1 week after streptozotocininjection), and the adipose tissue-absent diabetic rat liver. In conclusion: 1) enhanced f3-adrenergic, and decreased glucagon-or secretin-induced CAMP production seems to be caused by different mechanisms; 2) the prolonged severe diabetic state losing adipose tissue may cause a considerable change in metabolism and the characteristics of hepatocyte, and lead to enhanced fl-adrenergic cAMP production.streptozotocin-induced diabetic rat liver; adenosine 3', 5'-monophosphate (CAMP); caecholamine; glucagon; secretin It is well known that catecholamines stimulate through al-and R2-adrenergic receptors. The relative receptors in the rat liver depends on age (Sherline et al. sex (Studer and Borle 1982) and pathological conditions. hepatic glycogenolysis potency of these two 1974; Blair et al. 1979),In the normal male rat

The amounts of glucagon-like materials in the cerebrospinal fluid (CSF) of the dog and man were measured by radioimmunoassays with C-terminal specific antibody (glucagon immunoreactivity, GI) and with non-specific antibody (glucagon-like immunoreactivity, GLI). The levels of GI and GLI in the canine cerebrospinal fluid were l5.4i2.7 pg/ml (meanj;SD) and 4l.3i7.5 pg/ml, respectively, and those in the human fluid were l3.4i0.3 pg/ml, and 20.8il.9 pg/ml, respectively. Transportation of intravenously administered 1251-glucagon to the cerebrospinal fluid was negligible and that of intraventricularly administered 1251-glucagon to the peripheral blood was only 0.070 to 0.072% of the given dosage. These findings could add to the evidence that the glucagon-like materials may be one of the brain peptides.