Abstract: GIP is a major physiological component of the enteroinsular axis. Several researchers have pointed to a neural regulation of GIP secretion. We have previously studied the effect of intracerebroventricular (icv) infusion of insulin, NPY and bombesin in the regulation of GIP secretion. The aim of the present study is to evaluate a possible role of neurotensin in neural regulation of GIP secretion. Thirty-two adult dogs were used in this study. In a dose-response study (experiment 1) we used 3 different doses of neurotensin (25, 50 and 100microg) in a bolus icv infusion. In experiment 2 the animals received a bolus icv infusion of 50microg neurotensin and an equivalent amount of artificial cerebrospinal fluid (aCSF) at 1-week interval. In experiment 3 the animals received a continuous icv infusion of neurotensin at a constant rate of 1microg/kg/h and aCSF over a 3-h period, at 1-week interval. In experiment 4 the experiment of group 3 was repeated with a simultaneous intraduodenal infusion of a glucose load through the Mann-Bollman fistula. Plasma levels of glucose, insulin and GIP were assayed. Results: Bolus and continuous icv infusion of neurotensin produced a significant increase in glucose, GIP and insulin levels. In the 4th experiment icv infusion of neurotensin produced a more prominent increase of glucose and insulin levels compare to infusion of aCSF. GIP levels were lower after infusion of neurotensin compared to aCSF. Conclusions: Our data suggest a differential effect of neurotensin on GIP secretion, dependent on the energy load.
Abstract: Glucose-dependent insulinotropic polypeptide (GIP) is an incretin with important role in glucose homeostasis and energy conservation. Thus far, the neural mechanisms involved in the regulation of GIP secretion, have not yet been fully elucidated. The aim of this study was to evaluate a possible effect of intracerebroventricular administration of Bombesin in the regulation of GIP secretion. METHODS: Thirty-two adult dogs were used in this study. In group 1 the animals received a bolus icv infusion of 200 ng bombesin or an equivalent amount of artificial cerebrospinal fluid (aCSF). In group 2 the animals received a continuous icv infusion of bombesin or aCSF over a 3-h period. In group 3 the experiment of group 2 was repeated with a simultaneous intraduodenal infusion of a glucose load through the Mann-Bollman fistula. Blood samples were taken from cannulation of a hind limb and plasma levels of glucose, insulin and GIP were assayed. RESULTS: Bolus icv infusion of bombesin produced an increase in glucose and GIP levels without a respective increase in plasma insulin levels. Continuous icv infusion and the simultaneous infusion of glucose intraduodenally increased significantly GIP, glucose and insulin levels. CONCLUSIONS: Intracerebroventricular levels of bombesin seems to involve in the neural regulation of GIP secretion independently of the presence of nutrients and to potentiate GIP secretion during a glucose load.
Abstract: Intracerebroventricular (icv) injection of neuropeptide Y (NPY), which is a widely-distributed neurotransmitter, into the paraventricular nuclear area has been shown previously to increase secretion of insulin and glucagon from the pancreatic islets. Vasoactive intestinal polypeptide (VIP) is a 28-amino-acid peptide that is associated with the mobilisation of energy during situations of energy depletion, such as fasting and exercise. VIP has also been reported to alter insulin and glucagon levels in a glucose-dependent manner. The aim of this study was to determine whether icv infusion of NPY affected VIP secretion in dogs. Intracerebroventricular injections (0.5 ml) were administered through a stereotactic apparatus to six healthy dogs. This prototype epicranial apparatus was positioned surgically to allow the easy and exact localisation of the third ventricle for infusion or sampling. Doses of 5, 10, and 25 microg NPY, dissolved in artificial cerebrospinal fluid (aCSF), were infused for a total of 30 min using a Harvard infusion pump. For control experiments, aCSF alone was injected. Blood samples were taken 15 min before icv injection (basal), immediately after injection, and at 5, 10, 15, 30, 45, 60, 90, and 120 min after, to determine the levels of glucose, insulin, glucagon, and VIP. Intracerebroventricular infusion of NPY resulted in a short-term increase in VIP secretion, followed by a more gradual and lengthier decrease in VIP levels. The secretion of insulin and glucagon increased significantly with all three doses of NPY. Intracerebroventricular infusion of NPY increased secretion of insulin and glucagon from the pancreas. The rapid change in the levels of VIP suggested the possibility of neural regulation by NPY.
Abstract: We studied the effects on blood lipids and physical fitness after a training program that combined strength and aerobic exercise in postmenopausal women with type 2 diabetes. Ten patients (55.0 +/- 5.2 years) followed four exercise sessions per week, two strength and two aerobic, and ten (59.4 +/- 3.2 years) served as a control group. Lipid profile, glycated hemoglobin (HbA(1c)), HOMA2 index, exercise stress and muscular testing were assessed at the beginning and after 16 weeks of training program. Exercise training increased significantly HDL-C (17.2%; P < 0.001) and decreased triglycerides (18.9%), HbA(1c) (15.0%), fasting plasma glucose (5.4%), insulin resistance (HOMA2 25.2%) and resting blood pressure (P < 0.01). After 16 weeks of training, exercise time (17.8%) and muscular strength increased significantly (P < 0.001). The results indicated that a combined strength and aerobic training program could induce positive adaptations on lipid profile, glycemic control, insulin resistance, cardiovascular function, and physical fitness in post-menopausal women with type 2 diabetes.
Abstract: Glucose-dependent insulinotropic polypeptide (GIP), is an incretin with important role in glucose homeostasis and energy conservation. Thus far, the neural/hormonal mechanisms involved in the regulation of GIP secretion, have not yet been fully elucidated. The aim of this study was to evaluate a possible effect of intracerebroventricular administration of insulin in a centrally mediated regulation of GIP. Methods: Twenty-four adult dogs were used in this study. In group 1 the animals received a bolus icv infusion of regular insulin in a total volume of 50 microl or an equivalent amount of artificial cerebrospinal fluid (aCSF). In group 2 the animals received a continuous icv infusion of insulin or aCSF over a 3-h period. In group 3 the experiment of group 2 was repeated with a simultaneous intraduodenal infusion of a glucose load through the Mann-Bollman fistula. Blood samples were taken from cannulation of a hind limb vein at -15, 0, 5, 10, 15, 30, 45, 60, 90, 120, 150 and 180 min after infusions. Plasma levels of glucose, insulin and GIP were assayed. Results: Insulin levels were increased significantly in group 2 and 3 while GIP secretion was partly inhibited after icv administration of insulin and intraduodenal administration of glucose in the 3rd group. Conclusions: It is suggested that the hypothalamic insulin signaling contributes to plasma insulin levels and possibly exerts a negative regulation of GIP secretion after glucose load.
Abstract: The rapid increase of incretins glucose-dependent insulinotropic peptide (GIP) and glucagon like peptide-1 (GLP-1), within 5-15min, after food ingestion, suggests that a neural mechanism might be involved in the regulation of their secretion. The aim of this study is to determine whether intracerebroventricular (i.c.v) administration of neuropeptide Y (NPY), a widely distributed neurotransmmiter, can mediate this neural regulation of GIP secretion after food consumption. Six healthy mongrel dogs were utilized for this study. A prototype epicranial apparatus was placed surgically, allowing easy and exact localization of the third ventricle for infusions or sampling. Simultaneous blood sampling was obtained from cannulation of a hind limb vein. Plasma insulin, and GIP concentrations were measured after i.c.v infusion of 5, 10 and 25mug of NPY dissolved in 0.5ml of artificial cerebrospinal fluid (a CSF). The secretion of GIP and insulin were increased after the injection of NPY in a different pattern. Our data indicate that NPY might be involved in a possible neural control mechanism of GIP secretion after food consumption.
Abstract: OBJECTIVE: To determine the effect of treatment with vitamin D(3) analogue in the parameters of glucose metabolism in obese women with polycystic ovary syndrome (PCOS). DESIGN: Observational study. SETTING: Obese women with PCOS in an academic research environment. PATIENT(S): Fifteen obese women (mean age 28 +/- 1.3 years, mean body mass index 32.55 +/- 0.43) with documented chronic anovulation and hyperandrogenism were recruited into the study. INTERVENTION(S): Alphacalcidol (1-alpha-hydroxyvitamin D(3)) was administered orally 1 mug/day for 3 months. All subjects underwent a frequently sampled IV glucose tolerance test after a 10- to 12-hour overnight fast during a spontaneous bleeding episode before and after treatment with alphacalcidol. MAIN OUTCOME MEASURE(S): Peripheral insulin resistance and insulin effectiveness were estimated with minimal model. RESULT(S): The first phase of insulin secretion was significantly increased after treatment with alphacalcidol. A favorable statistically significant change also was observed in the lipid profile. CONCLUSION(S): Treatment with the vitamin D(3) analogue (alphacalcidol) could be of value in the management of PCOS.
Abstract: The purpose of the present study was to investigate the short- and long-term effects of a combined strength and aerobic training program on glycemic control, insulin action, exercise capacity and muscular strength in postmenopausal women with type 2 diabetes. Nine postmenopausal women, aged 55.2 (6.7) years, with type 2 diabetes participated in a supervised training program for 4 months consisting of two strength training sessions (3 sets of 12 repetitions at 60% one-repetition maximum strength) and two aerobic training sessions (60-70% of maximum heart rate at the beginning, and 70-80% of maximum heart rate after 2 months). Anthropometrical measurements, percentage glycated hemoglobin, a 2-h oral glucose tolerance test, exercise stress testing and maximum strength were measured at the beginning, and after 4 and 16 weeks of the exercise program. Significant reductions were observed in both the glucose (8.1% P<0.01) and insulin areas under the curve (20.7%, P<0.05) after 4 weeks of training. These adaptations were further improved after 16 weeks (glucose 12.5%, insulin 38%, P<0.001). Glycated hemoglobin was significantly decreased after 4 weeks [7.7 (1.7) vs 7.1 (1.3)%, P<0.05] and after 16 weeks [7.7 (1.7) vs 6.9 (1.0)%, P<0.01] of exercise training. Furthermore, exercise time and muscular strength were significantly improved after 4 weeks (P<0.01) as well as after 16 weeks (P<0.001) of training. Body mass and body-mass index, however, were not significantly altered throughout the study. The results indicated that a combined training program of strength and aerobic exercise could induce positive adaptations on glucose control, insulin action, muscular strength and exercise tolerance in women with type 2 diabetes.
Abstract: A polymorphism in codon 52 of the human thyrotropin receptor results in a proline to threonine substitution in the extracellular domain of the receptor, and it has been suggested that the rarer, 52Thr, allele is associated with susceptibility to Graves' disease in the female population. To investigate this association we analyzed the distribution of TSH-R alleles in male (n = 60) and female (n = 120) Graves' patients, and control subjects (male n = 160 and female n = 85), using a PCR amplification and mismatch oligonucleotide hybridization technique. The variant allele was present in 8.3% of patients and 7.3% of control subjects. The frequencies in male and female patients were 6.7 and 9.2% respectively, and the allele distribution did not differ significantly from that observed in controls. No association was found between this TSH-R polymorphism and the occurrence of Graves' disease in the male or female population.
Abstract: OBJECTIVE: The autoimmune thyroid diseases, Graves disease and autoimmune hypothyroidism, result from a complex interaction between genetic, environmental and endogenous factors. The genetic loci conferring susceptibility remain unclear. A recent report has demonstrated an association between a microsatellite polymorphism of the CTLA-4 gene (allele 106) on chromosome 2q33 and Graves' disease in Caucasian patients in the USA. The aim of the present study was to confirm this association in UK patients and to determine whether this polymorphism is also associated with autoimmune hypothyroidism. DESIGN: Analysis of Caucasian patients with autoimmune thyroid disease from a single clinic, compared to local Caucasian controls. PATIENTS: We studied 112 patients with Graves' disease, 44 with autoimmune hypothyroidism and 91 controls. MEASUREMENTS: CTLA-4 microsatellite gene polymorphisms were determined by polymerase chain reaction amplification of genomic DNA and resolution of the products on sequencing gels. RESULTS: As in previous studies, 21 alleles of the CTLA-4 microsatellite region were detected. Allele 106 was significantly increased in patients with Graves' disease (P = 0.006) and in those with autoimmune hypothyroidism (P = 0.02) when compared to controls. There was no significant difference between the groups in the distribution of the other alleles and no association between allele 106 and sex, HLA-DR or -DQ specificities or the presence of ophthalmopathy in the Graves' patients. CONCLUSIONS: These results confirm that the CTLA-4 gene, or one closely associated with it, confers susceptibility to Grave's disease but is not specific as the CTLA-4 106 allele is also associated with autoimmune hypothyroidism. This association seems to be with autoimmune thyroid disease in general.
Abstract: Extramedullary haematopoiesis is sometimes encountered in severe anaemia. Rarely, it may cause neurological symptoms, leading to spinal cord or cauda equina compression. Three patients with thalassaemia intermedia, who developed neurological complications, are described. The diagnoses were based on the clinical findings, computed tomography and magnetic resonance imaging. Small doses of radiotherapy (10-20 Gy in 5-10 fractions) relieved symptoms in all of these patients. Our experience supports the role of radiation therapy as a treatment for this complication.
