Biology of Incretins: GLP-1 and GIP

Glucagon-like peptide 1 (GLP-1) is a 30-amino acid peptide hormone produced in the intestinal epithelial endocrine L-cells by differential processing of proglucagon, the gene which is expressed in ...

The Physiology of Glucagon-like Peptide 1

I. Introduction II. History of the Incretin Concept: Discovery of Gastric Inhibitory Polypeptide III. Discovery of GLP-1 IV. Structures of GLPs and Family of Glucagon-Related Peptides V. Tissue Distribution of the Expression of GLPs A. Pancreatic α-cells B. Intestinal L cells C. Central nervous system VI. Proglucagon Biosynthesis A. Organization/structure of the proglucagon gene B. Regulation of glucagon gene expression C. Posttranslational processing of proglucagon VII. Regulation of GLP Secretion A. Overview B. Intracellular signals C. Carbohydrates D. Fats E. Proteins F. Endocrine G. Neural H. GLP-2 VIII. Metabolism of GLPs A. GLP-1 B. GLP-2 IX. Physiological Actions of GLPs A. Overview B. Pancreatic islets C. Counterregulatory actions of GLP-1 and leptin on β-cells D. Stomach E. Lung F. Brain G. Liver, skeletal muscle, and fat H. Pituitary, hypothalamus, and thyroid I. Cardiovascular system J. GLP-2 X. GLP Receptors A. Structure B. Signaling C. Distribution D. Regulation E. GLP-2 XI. Pathophysiology o...

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The glucagon-like peptides.

We examined the effect of intravenously infused glucagon-like peptide 1 (GLP-1) on subjective appetite sensations after an energy-fixed breakfast, and on spontaneous energy intake at an ad libitum lunch. 20 young, healthy, normal-weight men participated in a placebo-controlled, randomized, blinded, crossover study. Infusion (GLP-1, 50 pmol/ kg.h or saline) was started simultaneously with initiation of the test meals. Visual analogue scales were used to assess appetite sensations throughout the experiment and the palatability of the test meals. Blood was sampled throughout the day for analysis of plasma hormone and substrate levels. After the energy-fixed breakfast, GLP-1 infusion enhanced satiety and fullness compared with placebo (treatment effect: P < 0.03). Furthermore, spontaneous energy intake at the ad libitum lunch was reduced by 12% by GLP-1 infusion compared with saline (P = 0.002). Plasma GLP-1, insulin, glucagon, and blood glucose profiles were affected significantly by the treatment (P < 0.002). In conclusion, the results show that GLP-1 enhanced satiety and reduced energy intake and thus may play a physiological regulatory role in controlling appetite and energy intake in humans.

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Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans.

The influence of dietary fiber on energy regulation remains controversial. This review summarizes published studies on the effects of dietary fiber on hunger, satiety, energy intake, and body composition in healthy individuals. Under conditions of fixed energy intake, the majority of studies indicate that an increase in either soluble or insoluble fiber intake increases postmeal satiety and decreases subsequent hunger. When energy intake is ad libitum, mean values for published studies indicate that consumption of an additional 14 g/day fiber for >2 days is associated with a 10% decrease in energy intake and body weight loss of 1.9 kg over 3.8 months. Furthermore, obese individuals may exhibit a greater suppression of energy intake and body weight loss (mean energy intake in all studies was reduced to 82% by higher fiber intake in overweight/obese people versus 94% in lean people; body weight loss was 2.4 kg versus 0.8 kg). These amounts are very similar to the mean changes in energy intake and body weight changes observed when dietary fat content is lowered from 38% to 24% of energy intake in controlled studies of nonobese and obese subjects. The observed changes in energy intake and body weight occur both when the fiber is from naturally high-fiber foods and when it is from a fiber supplement. In view of the fact that mean dietary fiber intake in the United States is currently only 15 g/day (i.e., approximately half the American Heart Association recommendation of 25-30 g/day), efforts to increase dietary fiber in individuals consuming <25 g/day may help to decrease the currently high national prevalence of obesity.

Dietary Fiber and Weight Regulation

BACKGROUND: Hypersecretion of insulinotropic factors such as glucose dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1(7-36)amide (GLP-1) have been postulated to account for the hyperinsulinaemia of obesity. AIMS: To examine the role of GLP-1 and GIP in obese women and matched controls. SUBJECTS: Six lean and six obese women subjects matched for age. METHODS: The gut hormone, plasma glucose, and serum triglyceride responses were studied over 180 minutes after oral carbohydrate and fat meals. Heparin (10,000 units) was given intravenously at 120 minutes. RESULTS: There was pronounced attenuation of plasma GLP-1 secretion to oral carbohydrate in the obese compared with lean subjects but no such difference in response to oral fat load. There were no differences in the plasma GIP responses to carbohydrate or fat feeding. There was an apparent fall in plasma GLP-1 values in all subjects after administration of heparin. CONCLUSION: Postprandial GLP-1 secretion in response to oral carbohydrate is considerably attenuated in obese subjects. The cause of this attenuation of GLP-1 secretion is not known although we suggest that both this fall and the overall reduction in GLP-1 values in obese subjects may be related to an increase in plasma non-esterified fatty acids.

https://gut.bmj.com/content/gutjnl/38/6/916.full.pdf

L M Morgan

Papers

Attenuated GLP-1 secretion in obesity: cause or consequence?