Defective awakening response to nocturnal hypoglycemia in patients with type 1 diabetes mellitus.

Background: Nocturnal hypoglycemia frequently occurs in patients with type 1 diabetes mellitus (T1DM). It can be fatal and is believed to promote the development of the hypoglycemia-unawareness syndrome. Whether hypoglycemia normally provokes awakening from sleep in individuals who do not have diabetes, and whether this awakening response is impaired in T1DM patients, is unknown.

Intranasal insulin improves memory in humans: superiority of insulin aspart.

There is compelling evidence that intranasal administration of regular human insulin (RH-I) improves memory in humans. Owing to the reduced tendency of its molecules to form hexamers, the rapid-acting insulin analog insulin aspart (ASP-I) is more rapidly absorbed than RH-I after subcutaneous administration. Since after intranasal insulin administration, ASP-I may also be expected to access the brain, we examined whether intranasal ASP-I has stronger beneficial effects on declarative memory than RH-I in humans.

Persistent suppression of resting energy expenditure after acute hypoxia.

Resting energy expenditure (REE) is known to be influenced by various ambient conditions such as oxygen supply. Investigations in healthy subjects during acute hypoxia revealed a drop in REE, but persistent effects after hypoxia had ended have not been examined so far. Although indirect calorimetry is a well-established method to measure REE, it may lead to false conclusions when hyperventilation, rise in lactate or catecholamines, and decrease of food intake accompany hypoxia.

Hormonal, subjective, and neurocognitive responses to brief hypoglycemia in postmenopausal women and age-matched men with type 2 diabetes mellitus.

Sexual dimorphisms in hypoglycemic counterregulation are well documented in young healthy and type 1 diabetic subjects. Here, we questioned whether sex differences in counterregulation are present also in type 2 diabetic patients who are in a postmenopausal state. In an attempt to answer this question, we examined hormonal responses to a single-step hypoglycemic clamp (50 mg/dL) in 15 postmenopausal women and 15 age-matched men.

Cortisol correlates with metabolic disturbances in a population study of type 2 diabetic patients.

Objective: The prevalence of type 2 diabetes mellitus is increasing rapidly in industrialized countries, and adrenal glucocorticoids may intensify this disease. We sought to assess the relationship between diabetes-associated metabolic disturbances and cortisol concentrations in patients with type 2 diabetes.

Design: We investigated 190 type 2 diabetic patients who volunteered from a population study of 12,430 people in Luebeck and its suburbs.

Differential effects of hydrocortisone on sympathetic and hemodynamic responses to sympathoexcitatory manoeuvres in men.

Aim of the present study was to investigate the influence of hydrocortisone on muscle sympathetic nerve activity (MSNA) and hemodynamic parameters during different sympathoexcitatory manoeuvres in humans. The study focuses on the interaction of the hypothalamo-pituitary-adrenal system and the sympathetic nervous system. Hydrocortisone 100 mg or placebo was administered intravenously to eight young healthy subjects in a double-blind crossover design.

Unusual presentation of hypophysitis preceding an empty sella in a 75-year-old woman.

A 75-year-old woman complained about progressing fatigue. She appeared somnolent, but fully oriented and in no acute distress. Her face was pale and puffy.

Overweight humans are resistant to the weight-reducing effects of melanocortin4-10.

Context: By enhancing energy expenditure and suppressing appetite, melanocortin peptides derived from proopiomelanocortin play a primary role in the hypothalamic regulation of body weight. In a recent study in normal-weight adults, the 6-wk intranasal administration of the MSH/ACTH(4-10) core fragment of proopiomelanocortin resulted in a distinct reduction of body weight and body fat, accompanied by significant decreases in leptin and insulin plasma concentrations.

Objective: The present study aimed to generalize this finding to overweight patients.

Modulation of food intake by glucose in patients with type 2 diabetes.

Objective: A gain in body weight is a common adverse effect of glucose-lowering therapies in patients with type 2 diabetes, the mechanisms of which are not completely understood. Blood glucose is considered to play a crucial role in the regulation of food intake. On this background, we hypothesized that a short-term reduction of blood glucose concentration to normal values acutely increases food intake in type 2 diabetic patients.

Acute hypoxia decreases plasma VEGF concentration in healthy humans.

Vascular endothelial growth factor (VEGF) is known to be upregulated by hypoxia in vitro. However, in vivo data about VEGF regulation in chronic hypoxic diseases are conflicting. We investigated the effects of hypoxia on plasma VEGF concentration in healthy subjects.

Immediate but not long-term intranasal administration of insulin raises blood pressure in human beings.

Intranasal administration of insulin has been shown to influence neuroendocrine functions via an effect on central nervous mechanisms. Because insulin, in particular when infused into cerebral arteries, induces blood pressure (BP) elevation by an unknown mechanism, we investigated whether insulin exerts similar effects on BP after intranasal administration. To evaluate the immediate effects of insulin on BP, 20 IU of human insulin was intranasally administered every 10 minutes over a 2-hour period.

Changes in blood pressure and plasma catecholamine levels during prolonged hyperinsulinemia.

Hyperinsulinemia has been shown to induce activation of the sympathetic nervous system and vasodilatation. Whether these effects result in changes in blood pressure (BP) is discussed controversially. We measured BP and plasma catecholamine levels in 30 healthy men during a 60-minute baseline phase and 360-minute period of insulin infusion.

Processing of food stimuli is selectively enhanced during insulin-induced hypoglycemia in healthy men.

Recently it has been reported that during insulin-induced hypoglycemia selective attention is directed to food stimuli suggesting an adaptive cognitive strategy to escape from this potentially dangerous metabolic state. Here, we tested this hypothesis using a short-term memory task. We also aimed to define a hypoglycemic threshold level at which such an adaptive cognitive strategy first occurs.

Preserved inhibitory effect of recurrent hypoglycaemia on the male gonadotrophic axis.

Objective: Hypoglycaemia-induced decreases in male LH and testosterone concentrations are possibly mediated by activation of the hypothalamus-pituitary-adrenal (HPA) axis or by an increase in PRL. As counterregulatory stress hormone release is attenuated during recurrent hypoglycaemia, we questioned whether the gonadotrophic axis and PRL adapt similarly.

Design: We performed two consecutive hypoglycaemic clamps on day 1 and one clamp on the following day in 15 healthy men.

Gut protein uptake and mechanisms of meal-induced cortisol release.

The enhanced cortisol release after protein-rich meals might represent a neuroendocrine response to food allergens. We tested whether the antigenicity of proteins contributes to this effect. Twelve healthy men nasogastrically received casein, its less allergenic hydrolysate, and placebo.

Preserved circadian rhythm of serum insulin concentration at low plasma glucose during fasting in lean and overweight humans.

Circadian rhythms in glucose metabolism are well documented. Most studies, however, evaluated such variations under conditions of continuous glucose supply, either via food intake or glucose infusion. Here we assessed in 30 subjects circadian variations in concentrations of plasma glucose, serum insulin, and C-peptide during a 72-hour fasting period to evaluate rhythms independent from glucose supply.

Elevated resting and exercise-induced cortisol levels after mineralocorticoid receptor blockade with canrenoate in healthy humans.

Activation of central nervous mineralocorticoid receptors (MRs) has been shown to inhibit the activity of the hypothalamo-pituitary-adrenocortical (HPA) axis in animals. Here, we examined whether MRs in humans likewise regulate HPA activity in response to a physiological stressor. In a balanced, randomized, double-blind, cross-over trial, 12 healthy men were treated with either two injections of 200 mg canrenoate or placebo 24 and 8 h before an intense physical exercise taking place between 1600 and 1700 h.

Intranasal atrial natriuretic peptide acts as central nervous inhibitor of the hypothalamo-pituitary-adrenal stress system in humans.

Increased hypothalamo-pituitary-adrenal activity contributes to morbidity in widespread metabolic and psychiatric diseases. Inhibition of hypercortisolism represents a promising therapeutic strategy in these conditions, which currently cannot be used. Here, we tested the hypothesis that atrial natriuretic peptide (ANP) administered intranasally is a safe and feasible inhibitor of pituitary-adrenal activity at the central nervous level.

Transcortical direct current potential shift reflects immediate signaling of systemic insulin to the human brain.

Circulating insulin is thought to provide a major feedback signal for the hypothalamic regulation of energy homeostasis and food intake, although this signaling appears to be slowed by a time-consuming blood-to-brain transport. Here we show, by recording direct current potentials, a rapid onset of the effects of circulating insulin on human brain activity. Recordings were obtained from 27 men who were intravenously injected with insulin (0.

Intranasal insulin improves memory in humans.

Previous studies have suggested an acutely improving effect of insulin on memory function. To study changes in memory associated with a prolonged increase in brain insulin activity in humans, here we used the intranasal route of insulin administration known to provide direct access of the substance to the cerebrospinal fluid compartment. Based on previous results indicating a prevalence of insulin receptors in limbic and hippocampal regions as well as improvements in memory with systemic insulin administration, we expected that intranasal administration of insulin improves primarily hippocampus dependent declaration memory function.

Differences between nighttime and daytime hypoglycemia counterregulation in healthy humans.

Disturbances in hormonal counterregulation may be the main reason why many type 1 diabetic patients are asymptomatic during nighttime hypoglycemia. While it is known that sleep attenuates counterregulatory responses to hypoglycemia, the influence of the time of day on hormonal counterregulation regulation remains obscure. We induced hypoglycemia at 2 different time intervals, ie, in the morning and in the early night, in healthy subjects staying awake throughout the experiments.

Sleep associated regulation of T helper 1/T helper 2 cytokine balance in humans.

Recent human studies suggested a supportive influence of regular nocturnal sleep on immune responses to experimental infection (vaccination). We hypothesized here that sleep could ease such responses by shifting the balance between T helper 1 (Th1) and T helper 2 (Th2) cytokine activity towards Th1 dominance thereby favoring cellular over humoral responses to infection. We compared the Th1/Th2 cytokine balance in 14 healthy men during regular nocturnal sleep (between 23:00 and 07:00 h) and while remaining awake during the same nocturnal interval, in a within-subject cross-over design.

Hypoxia causes glucose intolerance in humans.

Hypoxic respiratory diseases are frequently accompanied by glucose intolerance. We examined whether hypoxia is a cause of glucose intolerance in healthy subjects. In a double-blind within-subject crossover design, hypoxic versus normoxic conditions were induced in 14 healthy men for 30 minutes by decreasing oxygen saturation to 75% (versus 96% in control subjects) under the conditions of a euglycemic clamp.

Melatonin acutely improves the neuroendocrine architecture of sleep in blind individuals.

In blind individuals, the absence of light cues results in disturbances of sleep and sleep-related neuroendocrine patterns. The Zeitgeber influence of light on the timing of sleep is assumed to be mediated by melatonin, a hormone of the pineal gland, whose secretion is inhibited by light and enhanced during darkness. Here, we investigated whether a single administration of melatonin improves sleep and associated neuroendocrine patterns in blind individuals.