Differential effects of IGF-I and insulin on glucoregulation and fat metabolism in depancreatized dogs

The effects of equipotent glucose-lowering doses of insulinlike growth factor I (IGF-I) and insulin on tracer-determined glucose kinetics and several metabolites were compared in 14 experiments (7 in each group) in fasted, totally depancreatized dogs. This model prevented variations in insulin secretion induced by IGF-I and permitted evaluation of the effects of IGF-I on extrapancreatic glucagon. Steady-state moderate hyperglycemia (9.9 +/- 0.2 mM) was maintained by a subbasal intraportal infusion of insulin (1.29 +/- 0.17 pmol.kg-1.min-1). This was continued throughout the experiment, allowing evaluation of IGF-I effects on insulin clearance. Human recombinant IGF-I or insulin was given intravenously as a primed infusion for 90 min, followed by a 50-min recovery period. The dose of IGF-I was a 2.6-nmol/kg bolus plus 57.4 pmol.kg-1.min-1. The insulin dose required to induce the same plasma glucose decline as IGF-I (44 +/- 6 vs. 43 +/- 5%, NS) was 9-12 times lower (0.06-nmol/kg bolus + 6.4 +/- 0.6 pmol.kg-1.min-1). However, the mechanism of this decline differed with IGF-I and insulin; glucose production was much less suppressed (25 +/- 9 vs. 42 +/- 11%, P less than 0.001) and glucose utilization was more stimulated (68 +/- 18 vs. 38 +/- 19%, P less than 0.05) with IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)     

IgG subclasses, barrier function for albumin and production of immunoglobulin G in the central nervous system

Cerebrospinal fluids from patients with neurological diseases have been studied. It appeared that the detectability of immunoglobulin G subclasses 1, 2, 3, 4, and the occurrence of oligoclonal bands in the IgG region increased with increasing concentration of IgG in the spinal fluid. No specific pattern emerged in the different disease groups. Formula: see text.     

Vitamin D deficiency and rickets in the Eastern Province of Saudi Arabia

BACKGROUND: Nutritional rickets remains prevalent in many developing countries, despite the availability of ample sunlight. The aim of this study was to investigate the clinical features and chemical pathology in a group of children with rickets and to compare them with a control group. SUBJECTS AND METHODS: In a case-control study over a 1-year period (March 2004 to February 2005), children clinically diagnosed with rickets (n=61) were age- and sex-matched with controls (n=58). In addition to routine chemical pathology, 25 (OH) vitamin D3 and parathormone (PTH) were determined. Controls were children without clinical rickets attending hospital for other blood investigations. RESULTS: The mean age of children with rickets was 14.8 mths and of controls was 16.5 mths. Mean (SD) body mass index of the children with rickets [16.8 (1.86)] was not significantly different from that of the controls [17.02 (3.16)]. Mean (SD) head circumference of rachitic children [45.41 (3.64) cm] was greater than that of controls [44.39 (5.07) cm, p=0.03]. Eighty per cent of the children with rickets were breastfed compared with 67% of controls. Thirty per cent of children with rickets were hypocalcaemic vs <7% of controls, 89% had phosphorus values <1.5 mmol/L vs 34.5% of controls and 75% had alkaline phosphatise levels >500 IU/L vs 28% of controls. Seventy-five per cent of children with rickets had serum 25 (OH) D3 <20 nmol/L vs 25% of controls. Mean (SD) PTH level was 23.59 (19.03) pmol/L in the rachitic group and 1.9 (1.05) pmol/L in controls (p<0.05). Lack of exposure to sunlight was recorded in 90% of the children with rickets and in 37% of the controls. CONCLUSION: Apparently healthy children living in areas where rickets is prevalent have risk factors for rickets and a small proportion will have evidence of biochemical rickets.     

Pancreastatin-like immunoreactivity and insulin are released in parallel from the perfused porcine pancreas

Pancreastatin, a peptide isolated from the porcine pancreas, suppresses insulin release from pancreatic islets of the rat. Pancreastatin immunoreactivity has been localized to islet B and D cells in the porcine pancreas. We have developed a RIA for this peptide, using rabbit anti-porcine pancreastatin antibodies and 125I-Tyr-pancreastatin. Isolated pig pancreata were perfused with a nonrecirculating bicarbonate buffer solution containing 4% Dextran and 0.1% Albumin. Glucose (11 mmol/liter) induced a biphasic release of pancreastatin-like immunoreactivity (PLI). Electrical stimulation of the vagus nerves (8 Hz), as well as perfusion with acetyl choline (10(-6) mol/liter) in the presence of 5.5 mmol/liter glucose, also evoked prompt PLI responses. Furthermore, truncated GLP-1 (proglucagon 78-107; 10(-9) mol/liter) induced PLI release. All tested stimuli also elicited insulin secretion. To investigate whether the PLI measured could be ascribed to secretion of the low molecular weight pancreastatin (Mr 5,100) or to a possible precursor such as chromogranin A (Mr approximately 75,000), perfusates containing PLI were subjected to gel filtration on an Ultropac G3000SW column. All of the PLI was recovered at the elution position of the pancreastatin marker. In conclusion, PLI and insulin are released in parallel from the perfused porcine pancreas, exposed to stimuli known to affect insulin release.     

Effects of cholecystokinin (CCK)-8, CCK-33, and gastric inhibitory polypeptide (GIP) on basal and meal-stimulated pancreatic hormone secretion in man.

Gastrointestinal hormones with insulinotropic effects, like cholecystokinin (CCK) and gastric inhibitory polypeptide (GIP) might tentatively be used in the treatment of non-insulin-dependent diabetes mellitus. We therefore examined the effects of intravenous injection of pharmacological dose levels of CCK-8 (100 and 300 pmol/kg), CCK-33 (100 pmol/kg), GIP (100 pmol/kg), and CCK-8 plus GIP (100 pmol/kg of each) on plasma levels of glucose, insulin, somatostatin, glucagon, and pancreatic polypeptide (PP) in healthy human volunteers. The peptides were given under basal conditions or in combination with a mixed meal. CCK-8, CCK-33, and GIP were all found to increase the basal plasma levels of insulin, somatostatin, and PP; the increases were observed already in samples taken at 2 min after the injection. In contrast, the plasma glucagon levels were unaffected by the peptides. CCK-8, CCK-33, and GIP (100 pmol/kg) all potentiated the meal-induced plasma responses of insulin and PP, whereas plasma levels of glucagon after the meal were not affected. Plasma somatostatin levels after the meal were increased by GIP but not affected by CCK-8 or CCK-33. CCK-8 and GIP together (100 pmol/kg for both) increased plasma levels of insulin, PP and somatostatin as much as each of the peptides given alone, both under basal conditions and after the meal intake. Plasma levels of glucagon were not affected by CCK-8 and GIP together. We conclude that in man, both CCK-8, CCK-33, and GIP moderately stimulate basal and meal related insulin release without any synergistic effects and that the peptides do not inhibit the secretion of glucagon.