|
|||||||||
 |
Glucagon-like Peptide 1 related products |
Glucagon-like peptide 1 as a regulator of food intake and body weight: therapeutic perspectives
After ingestion of carbohydrate- and fat-rich meals, the incretin hormone glucagon-like peptide 1 (GLP-1) is secreted from the L-cells in the distal put into the circulation. Its major physiological effect lies in a strongly glucose-dependent stimulation of insulin secretion from pancreatic B-cells. Furthermore, GLP-1 suppresses glucagon secretion, stimulates B-cell neogenesis as well as proinsulin biosynthesis and inhibits gastric emptying and acid secretion. Recently, GLP-1 could be shown to reduce caloric intake and to enhance satiety, most likely via specific receptors within the central nervous system, resulting in reduced weight gain in experimental animals. In nondiabetic and Type 2 diabetic human subjects, exogenous GLP-1 reduces hunger, caloric intake and body weight. Therefore, in addition to its well-characterized antidiabetogenic effect, the anorectic effect may offer GLP-1 a potential in the pharmacotherapy of obesity. It is still unknown whether the GLP-1 effect on caloric intake is sustained after long-term treatment. Furthermore, the exact mechanisms by which the peptide exerts its biological effects have not yet been clarified. Due to the rapid degradation of native GLP-1, its therapeutic application is limited by the short half-life. Therefore, suitable modes of administration are needed in order to reach stable plasma concentrations. The present review aims to describe the role of GLP-1 in the central regulation of feeding and to discuss its possible application in the pharmacotherapy of obesity.
Meier JJ, Gallwitz B, Schmidt WE, Nauck MA. Glucagon-like peptide 1 as a regulator of food intake and body weight: therapeutic perspectives. Eur J Pharmacol 2002 Apr 12;440(2-3):269-79
GLP-1 as a Satiety Factor in Children with Eating Disorders
GLP-1, with its insulinotropic properties and direct action on satiety center in the brain, may be the main hormone regulating the amount of ingested food. In this study, GLP-1 secretion was investigated in age-matched adolescent girls (14 +/- 2 years): 13 with anorexia nervosa (BMI 14.8 +/- 1.4 kg/m(2)), 13 with simple obesity (BMI 33.0 +/- 3.3 kg/m(2)) and 10 healthy girls as a control group (BMI 21.6 +/- 0.7 kg/m(2)). Each girl was subjected to OGTT and standard meal tests after a 12 h overnight fast. Blood samples were collected before and 15, 30, 60, and 120 min after the stimulation. The mean fasted GLP-1 levels in simple obesity group (1.6 +/- 0.3 pmol/l) and in anorexia nervosa group (1.7 +/- 0.3 pmol/l) were significantly lower than those in the control group (2.6 +/- 0.4 pmol/l) (p < 0.05 in both cases). The highest peak concentration of GLP-1 was observed in the control group after both stimuli. In each group, the mean integrated GLP-1 outputs were almost twice as high after OGTT than after the test meal (p < 0.001 in each case). In our opinion, low secretion of GLP-1 in girls with simple obesity may seriously and negatively influence the course of this disease. On the other hand, low GLP-1 levels in girls with anorexia nervosa are beneficial and promote appetite.
Tomasik PJ, Sztefko K, Malek A. GLP-1 as a Satiety Factor in Children with Eating Disorders. Horm Metab Res 2002 Feb;34(2):77-80
The gut and food intake: an update for surgeons
Food intake is the simplest and most obvious measure of gastrointestinal function, yet it rarely receives more than cursory attention from surgeons. In this review we cover recent findings on relationships between gut function and appetite regulation mediated via neuropeptides influenced by afferent and efferent vagal activity. Evidence from the new discipline known as neurogastroenterology elucidates gastric and intestinal signals involved in the elicitation of hunger, satiety, and aversion. Discovery of the adipose-tissue-derived hormone, leptin, has energized the field of metabolism spawning increasing numbers of publications related to interactions between leptin and insulin release and glucose disposal, as well as appetitive behavior. Peptides such as cholecystokinin (CCK), the proglucagon-derived peptides, glucagon-like peptides 1 and 2 (GLP-1 and GLP-2), and the recently identified powerful intake-stimulating molecule, orexin, are examples of potential targets for drug development and studies of surgical pathophysiology. A major conclusion of this work is that the considerable redundancy and overlap between mediators of caloric intake subserving survival of the species, while beneficial after foregut surgery, contribute to the complexity of treating the global epidemic of obesity. Possibly knowledge derived from basic research in neurogastroenterology can translate into advances in surgical treatment of obesity.
Naslund E, Hellstrom PM, Kral JG. The gut and food
intake: an update for surgeons. J Gastrointest Surg 2001 Sep-Oct;5(5):556-67
Glucagon-like peptide containing pathways in the regulation of feeding behaviour
The pre-proglucagon derived peptides, glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) are both involved in a wide variety of peripheral functions, such as glucose homeostasis, gastric emptying, intestinal growth, insulin secretion as well as the regulation of food intake. Pre-proglucagon is also found in the brainstem in a small population of nerve cells in the nucleus of the solitary tract (NTS) that process the pre-propeptide as in the gut to yield GLP-1 and GLP-2. GLP-1 containing nerve fibres and the GLP-1 receptor are found predominantly in hypothalamic midline nuclei. GLP-1 given centrally to naive rats results in a marked induction of c-Fos protein in the supraoptic nucleus, paraventricular nucleus of the hypothalamus (PVN) and central nucleus of the amygdala, but only a moderate increase in the arcuate nucleus. The pattern of c-Fos activation is compatible with the appetite suppressing effects of GLP-1. This anorectic effect of GLP-1 appears to be mediated by the PVN, as direct injections of GLP-1 into this nucleus cause anorexia without concomitant taste aversion, suggesting a specific action upon neuronal circuits involved in the regulation of feeding. Recent experiments have also shown that GLP-1 is implicated in mediating signals from the gastrointestinal tract pertaining to discomfort and malaise. The distribution of the co-localised peptide, GLP-2, displays a perfect overlap with GLP-1 in the CNS with the highest concentration in the diffuse ventral part of the dorsomedial nucleus (DMHv). In contrast to the widely distributed GLP-1 receptor mRNA, GLP-2 receptor mRNA is exclusively expressed in the compact part of the DMH (DMHc). Interestingly, the DMHc is also the only nucleus responding to central administration of GLP-2 with a significant increase in the number of c-Fos positive cells. When injected into the lateral ventricle, GLP-2 has a marked inhibitory effect on feeding. The effect of GLP-2 on feeding is both behaviourally and pharmacologically specific. Future experiments will elucidate whether or not GLP-1 and GLP-2 are involved in the long-term or short-term regulation of feeding behaviour and hence have an impact on bodyweight.
Tang-Christensen M, Vrang N, Larsen PJ. Glucagon-like
peptide containing pathways in the regulation of feeding behaviour. Int
J Obes Relat Metab Disord 2001 Dec;25 Suppl 5:S42-7
 |
 |
|
Glucagon-like Peptide 1 related products |