Intranasal insulin affects adenyl cyclase system in rat tissues in neonatal diabetes

The changes in hormone-regulated adenylyl cyclase (AC) signaling system implicated in control of the nervous, cardiovascular and reproductive systems may contribute to complications of diabetes mellitus (DM). We investigated the functional state of AC system in the brain, myocardium, ovary and uterus of rats with neonatal DM and examined the influence of intranasally administered insulin on the sensitivity of this system to biogenic amines and polypeptide hormones. The regulatory effects of somatostatin and 5-HT1BR-agonist 5-nonyloxytryptamine acting via Gi protein-coupled receptors were significantly decreased in DM and partially restored in insulin-treated rats. The effects of hormones, activators of AC, are changed in tissue- and receptorspecific manner, and intranasal insulin restored the effects rather close to the level in control. In insulin-treated non-diabetic rats, AC stimulating effects of isoproterenol and relaxin in the myocardium and of human chorionic gonadotropin in the ovaries were decreased, while the effects of hormones, inhibitors of AC, were increased. These data indicate that with intranasal insulin, Gi protein-mediated signaling pathways continue to gain strength. The obtained data on the influence of hormones on AC system in the brain, myocardium, ovary and uterus allow looking anew into the mechanisms of therapeutic effects of intranasal insulin.

Lanthanum: inhibition of ACTH-stimulated cyclic AMP and corticosterone synthesis in isolated rat adrenocortical cells.

Lanthanum (La+++) is a well-known Ca++ antagonist in a number of biological systems. It was used in the present study to examine the role of Ca++ in the regulation of adenyl cyclase of the adrenal cortex by ACTH. In micromolar concentrations, .La+++ inhibited both cyclic AMP and corticosterone response of isolated adrenal cortex cells to ACTH. However, a number of intracellular processes were not affected by La+++. These include the stimulation of steroidogenesis by dibutyryl cyclic AMP, conversion of several steroid precursors into corticosterone, and stimulation of the latter by glucose. Thus, inhibition of steroidogenesis by La+++ appears to be solely due to an inhibition of ACTH-stimulated cyclic AMP formation. Electron microscope examination showed that La+++ was localized on plasma membrane of the cells and did not appear to penetrate beyond this region. Since La+++ is believed to replace Ca++ at superficial binding sites on the cell membrane, it is proposed that Ca++ at these sites plays an important role in the regulation of adenyl cyclase by ACTH. Similarities in the role of Ca++ in "excitation-contraction" coupling and in the ACTH-adenyl cyclase system raise the possibility that a contractile protein may be involved in the regulation of adenyl cyclase by those hormones which are known to require Ca++ in the process.

A Study of the Neurohumoral Control of Glycolysis in the Mouse Brain in vivo: Role of Noradrenaline and Dopamine

Noradrenaline, Dopamine, Glycolysis, Adenyl Cyclase Intraventricularly injected noradrenaline, dopamine and isoprenaline increased glycolysis as shown by the decrease in the concentration of “free” glycogen and increase in the concentration of lactate. The effects of noradrenaline and isoprenaline were reduced in mice which had been pretreated with α-methyl-p-tyrosine. ʟᴅ-Propranolol blocked the increase in glycolysis caused by noradrenaline, isoprenaline, sodium fluoride and analogues of 3,5-cyclic adenosine monophosphate. It is suggested that the results of this investigation can be explained by the various drugs and neurohormones acting on the adenyl cyclase system in vivo, either by blocking the action of the neurohormone on the membrane bound enzyme or monophosphate on glycolysis.