A B S T R A C T The purpose of the present study was to investigate the regulation of insulin biosynthesis during the perinatal period. The incorporation of [3H]leucine into total immunoreactive insulin (IRI) and into IRI fractions was measured by a specific immunoprecipitation procedure after incubation, extraction, and gel filtration in isolated 3-day-old rat pancreases without prior isolation of islets. IRI fractions were identified by their elution profile, their immunological properties, and their ability to compete with the binding of "I-insulin in rat liver plasma membranes. No specific incorporation of [3H]leucine was found in the IRI eluted in the void volume, making it unlikely that this fraction behaves as a precursor of (pro)insulin in this system. In all conditions tested, the incorporation of [8H]leucine was linearly correlated with time. Optimal concentration of glucose (11 mM cose and was not modified by any further increase in glucose concentrations up to 27.5 mM. Theophylline or dbcAMP at 10 mM concentration did not reverse the somatostatin inhibitory effect on either insulin biosynthesis or release. Somatostatin also inhibited both processes in isolated islets from the 3-day-old rat pancreas. High Ca"+ concentration in the incubation medium reversed the inhibitory effect of somatostatin on glucoseinduced insulin biosynthesis as well as release. In both systems the inhibitory effect of somatostatin on insulin biosynthesis and release correlated well. Glipizide (10-100 ,M) and tolbutamide (400 ELM) inhibited the stimulatory effect of glucose, dbcAMP, and theophylline on [8H]leucine incorporation into IRI. The concentrations of glipizide that were effective in inhibiting [3H]leucine incorporation into IRI were smaller than those required to inhibit the phosphodiesterase activity in isolated islets of 3-day-old rat pancreas.These data suggest the following conclusions: (a) the role of the cAMP-phosphodiesterase system on insulin biosynthesis is likely to be greater in newborns than in adults; (b) the greater effectiveness of glucose and the cAMP system on insulin biosynthesis than on insulin release might possibly be related to the rapid accumulation of pancreatic IRI which is observed in the perinatal period; (c) somatostatin, by direct interaction with the endocrine tissue, can inhibit glucose and cAMPinduced insulin biosynthesis as well as release; calcium reverses this inhibition; (d) sulfonylureas inhibit insulin biosynthesis in newborn rat pancreas an effect which has

We have studied the binding of ml-GLP-l(7-36)amide to normal rat islet cells and rat insulinoma-derived RINm5F cells, and found it is time-and temperature-dependent, and directly proportional to cell concentration. In both cell types, the Scatchard plot demonstrates the presence of high-and low-affinity binding sites. The 50% inhibition of the maximal binding to 0.4 nM 1251-GLP-l(7-36)amide was obtained when cells were incubated in the presence of about 3.0 nM of unlabelled peptide. Glucagon, oxyntomodulin and GLP-l(7-36)amide at high concentrations (10 aM) do not compete with the 1251-GLP-l(7-36)amide binding. In pancreatic tumoral cells there seems to be a direct correlation between the maximal binding, the number of high-affinity binding sites and the amount of intracellular insulin.

IntroductionThe studies about the comorbidity of major depressive disorder (MDD) and bipolar disorder (BD) have increased in the last years. The comorbidity with Axis I psychiatric disorders complicates the diagnosis, prognosis and treatment.ObjectivesTo analyze the prevalence of affective disorders associated with another Axis I psychiatric disorders to treat correctly from the beginning of the diagnosis and to improve the course of the disorder and the quality of life of these patientsMethodsThe subjects who participated in the study were diagnosed of bipolar I disorder, bipolar II disorder and MDD, according to DSM-IV-TR criteria. The sample (n = 114) was divided into three groups: MDD (n = 58), BD (n = 31) and a control group of healthy subjects (n = 25). The diagnosis and stability were assessed using the MINI International Neuropsyquiatric Interview and the Hamilton Depression Rating Scale (HDRS).ResultsBD had a significantly association with risk of suicide (38%), anxiety disorder (3.3%) and social phobia (12.9%). It was also reported a significant association between MDD and risk of suicide (71%), manic/hypomanic episodes (25.9%), anxiety disorder (37.9%), social phobia (25.9%) and generalized anxiety disorder (37.9%).ConclusionsIt is necessary for clinical practice an integrative model which takes into account the comorbidity of affective disorders to improve the response to treatment and the prognosis of these mental disorders

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