Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the occurrence of parathyroid, pancreatic and pituitary tumors, and is due to mutations in the coding region of the MEN1 gene, which encodes menin. We investigated a family with identical twins that had MEN1, with different MEN1 tumors. DNA sequence analysis of the MEN1 coding region had not identified any abnormalities and we hypothesized that deletions and mutations involving the untranslated regions may be involved.
View Article and Find Full Text PDFFatigue and stress-related illnesses often become diagnoses of exclusion after extensive investigation. 'Tired all the time' is a frequent reason for referral to the endocrine clinic, the implicit question being--is there a subtle endocrine pathology contributing to the patient's symptoms? Often initial assessment suggests not but there are no clear data to address the question of whether overt pathology will develop in the future. This study observed outcomes after five years in 101 consecutive and unselected referrals to secondary care for 'fatigue?cause', where initial assessment did not suggest treatable endocrine pathology.
View Article and Find Full Text PDFBackground: The role of the autonomic nervous system in the complex link between insulin resistance and cardiovascular risk remains unclear. Increased sympathetic nervous system activity has been implicated in the pathophysiology of insulin resistance but is confounded by a number of factors.
Methods: We have therefore examined the relationship among cardiac autonomic control, insulin resistance, habitual physical activity, resting energy expenditure (REE), and anthropometric variables in a subset (107 boys, 101 girls, age 9 +/- 0.
Objectives: Leptin, an important hormonal regulator of body weight, has been shown to stimulate the sympathetic nervous system (SNS) in vitro although the physiological relevance remains unclear. Increased SNS activity has been implicated in the pathogenesis of insulin resistance and an increased cardiovascular risk. We have therefore investigated the relationship between leptin, insulin resistance and cardiac autonomic activity in healthy young adults.
View Article and Find Full Text PDFStudies of the effects of hypoglycemia on the brain using neurocognitive testing have suggested that mainly complex functions subserved by secondary and tertiary cortex are affected by mild to moderate hypoglycemia and that intensively treated patients with Type I diabetes mellitus (T1DM) may have altered sensitivity to the central nervous system effects of hypoglycemia. Functional magnetic resonance imaging provides a sensitive, regionally-specific probe of possible neurophysiologic changes related to hypoglycemia in the brain. Eleven intensively-treated T1DM patients and 11 matched non-diabetic controls took part in a 2-day protocol in which functional magnetic resonance imaging (MRI) was used to measure changes in the patterns of brain activation produced by simple auditory and visual stimuli in different conditions.
View Article and Find Full Text PDFIt has been postulated that specialized glucose-sensing neurons in the ventromedial hypothalamus (VMH) are able to detect falling blood glucose and trigger the release of counterregulatory hormones during hypoglycemia. The molecular mechanisms used by glucose-sensing neurons are uncertain but may involve cell surface ATP-sensitive K(+) channels (K(ATP) channels) analogous to those of the pancreatic beta-cell. We examined whether the delivery of sulfonylureas directly into the brain to close K(ATP) channels would modulate counterregulatory hormone responses to either brain glucopenia (using intracerebroventricular 5-thioglucose) or systemic hypoglycemia in awake chronically catheterized rats.
View Article and Find Full Text PDFWe have explored the role of individual elements of the hypothalamic pituitary adrenal axis on the pathogenesis of hypoglycemia-associated autonomic failure. Five groups of male Sprague-Dawley rats were used. Control animals had 3 days of sham treatment followed by a hyperinsulinemic/hypoglycemic glucose clamp on day 4.
View Article and Find Full Text PDFGhrelin is a novel peptide that acts on the growth hormone (GH) secretagogue receptor in the pituitary and hypothalamus. It may function as a third physiological regulator of GH secretion, along with GH-releasing hormone and somatostatin. In addition to the action of ghrelin on the GH axis, it appears to have a role in the determination of energy homeostasis.
View Article and Find Full Text PDFObjective: The MiniMed Continuous Glucose Monitoring System (CGMS) measures subcutaneous interstitial glucose levels that are calibrated against three or more fingerstick glucose levels daily. The objective of the present study was to examine whether the relationship between plasma and interstitial fluid glucose is altered by changes in plasma glucose and insulin levels and how such alterations might influence CGMS performance.
Research Design And Methods: Arterialized plasma glucose, sensor glucose, and interstitial fluid glucose were measured by microdialysis in 11 healthy subjects during a 1.