Seijiro Marubashi

Species difference of glucagon-like materials in the brain

Abstract Glucagon-like materials were found in the canine, porcine, bovine, rat and human brain. Both glucagon immunoreactivity measured with an antibody against the C-terminal portion of glucagon and glucagon-like immunoreactivity measured with an antibody against the N-terminal portion of glucagon were detected in the thalamus-hypothalamus, brain stem and spinal cord, but not in the cerebrum, basal ganglia, pituitary gland or cerebellum. The distribution of glucagon-like material in the brain was common in all tested mammals.

Modulation of plasma glucose levels by thyrotropin-releasing hormone administered intracerebroventricularly in the rat.

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.

Synaptosomal localization and release of glucagon-like materials in the rat brain

The subcellular localization of glucagon-like materials in the thalamus-hypothalamus and brain stem of the rat was investigated. Both glucagon immunoreactivity (GI) determined by C-terminal specific antibody and glucagon-like immunoreactivity (GLI) determined by non-specific antibody were enriched in the microsomal and synaptosomal fractions relative to the nuclear, myelin and mitochondrial fractions. Furthermore, the synaptosomal fraction of both the thalamus-hypothalamus and brain stem incubated in Krebs-Ringer bicarbonate buffer with 55 mM K+ at 37 degrees C released GI and GLI in the presence of Ca++. These findings suggested that glucagon-like substances detected in the brain have a role in the synaptic function.

Neuropeptides and Glucose Metabolism

In recent years, numerous new biologically active peptides have been discovered in the gastrointestinal tract. While immunohistochemical evidence suggests that at least 20 of them are present in the brain (1–3), their functions remain at issue since the effects of their direct intracerebral administration vary according to dose and experimental condition, and may include psychologic, neurologic, or autonomic functions, such as the emotions, consciousness and behavior, sensory and motor activity, libido, appetite, gut motility, blood pressure, respiration, body temperature, blood glucose, endocrine, and other functions. This chapter focuses on the role of some of these peptides in the central regulation of glucose metabolism.

125I-glucagon-degrading activity in acid-saline extracts of rat salivary gland

SummaryThe antibody-binding ability of the glucagon-like substance in rat submaxillary gland acid saline extract was examined by affinity chromatography, and the biological activity studied using the isolated liver perfusion method. We found that the glucagon-like substances in acid saline extract could not be bound to anti-glucagon antibody and that the gel-filtration peak on ultrogel AcA 54 could increase neither glucose nor cyclic AMP output from isolated perfused rat liver. Furthermore, the radioactivity peak of 125I-glucagon on Bio Gel P-6 column chromatography moved from its original position and eluted in later fractions after incubation with an acid saline extract of the submaxillary gland. In consequence, there was 125I-glucagon degrading activity in the submaxillary gland, but no glucagon-related peptide. Therefore, it is suggested that the glucagon-like substance, which has been reported in acid saline extract of the rat salivary gland, may be an artifact due to tracer degrading activity.