Glucagon and Glucagon‐like Peptide Production and Degradation

Kieffer, Timothy J.; Hussain, Mehboob A.; Habener, Joel F.

doi:10.1002/cphy.cp070208

Cited by 4 publications

(4 citation statements)

References 893 publications

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“…39,53 This likely occurs because the promoter region of the proglucagon gene, the gene for GLP-1, contains an ebox domain that is known to bind circadian transcription factors. 54 The molecular signaling necessary for these nutrient-induced changes have yet to be identified and the extent to which peripheral oscillators contribute to the release of the other gut peptides measured here is not clear.…”

Section: Discussionmentioning

confidence: 90%

Alterations in circadian and meal-induced gut peptide levels in lean and obese rats

Moghadam

Moran

Dailey

2017

Exp Biol Med (Maywood)

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Alterations in gut hormone signaling are a likely contributing factor to the metabolic disturbances associated with overweight/obesity as they coordinate the timing of feeding behavior, absorption, and utilization of nutrients. These hormones are released in response to food intake, or follow a circadian or anticipatory pattern of secretion that is independent of nutrient stimulation. The aim of this study was to identify the degree to which high-fat diet-induced obesity would alter the daily rhythm of gut peptide plasma levels (glucagon-like peptide-1 [GLP-1], peptide YY [PYY], insulin or amylin [AMY]) or meal-induced levels in the middle of the light or dark cycle. Male Sprague-Dawley rats were fed a high-fat diet (OBESE) or chow (LEAN), implanted with jugular catheters, and blood samples were taken every 2 h throughout the light/dark cycle while freely feeding or after an Ensure liquid meal. We found that even when OBESE and LEAN animals ate the same kcals and have a similar pattern of food intake, there is a difference in both the levels and rhythm of plasma gut peptides. GLP-1 and PYY are higher during the light cycle in LEAN animals and AMY is higher in the OBESE group throughout the light/dark cycle. There was also a differential response of plasma gut signals after the Ensure meal, even though the composition and amount of intake of the meal were the same in both groups. These changes occur prior to the high-fat diet induced loss of glycemic control and may be a target for early intervention. Impact statement The aim of this study was to test if obesity would alter the daily rhythm of gut peptides or meal-induced levels in the middle of the light or dark cycle. We found that even when animals are eating the same amount (in kcal) of food that the obese animals have altered daily rhythms and meal-induced gut peptide levels. In particular, we are the first to show that obesity induces increases in peptide YY levels during the light cycle and amylin remains high throughout the light and dark cycle in obese animals. These changes occurred prior to a loss of glycemic control. Thus, the rhythm of gut peptides could be used as an early indicator of later and more serious metabolic disturbances and may be a target for early intervention.

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Section: Discussionmentioning

confidence: 90%

Alterations in circadian and meal-induced gut peptide levels in lean and obese rats

Moghadam

Moran

Dailey

2017

Exp Biol Med (Maywood)

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“…The present study suggests that Ucn III acting through CRFR2 in the islet may represent a new intraislet regulatory mechanism that adds additional levels of modulation of insulin and glucagon secretion. It is interesting to note that Ucn III exhibits an opposite effect to that of somatostatin, raising the possibility that Ucn III may act to counterbalance somatostatin in mod- (37). In addition, hormones released from the islet under high glucose conditions, including insulin and somatostatin, may potentially mask the effects of Ucn III on glucagon secretion.…”

Section: Discussionmentioning

confidence: 97%

Urocortin III Is Expressed in Pancreatic β-Cells and Stimulates Insulin and Glucagon Secretion

et al. 2003

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Urocortin (Ucn) III, or stresscopin, is a high affinity ligand for the type 2 corticotropin-releasing factor (CRFR2) receptor recently identified in rodents and human. Ucn III was initially identified as a neuropeptide expressed in discrete areas in the brain. In the present study, we demonstrate that Ucn III is expressed in pancreatic beta-cells and in a mouse beta-cell line, MIN6. Ucn III secretion from the cells was measured using a highly specific RIA, and we found that high potassium, forskolin, or high glucose can stimulate Ucn III secretion from these cells. In vivo studies showed that rats receiving an iv Ucn III injection had a significant elevation of plasma glucagon followed by plasma glucose levels compared with rats receiving vehicle. Ucn III injections also result in an increase in plasma insulin levels. The observed effects of Ucn III were blocked by pretreatment with a CRFR2 antagonist, astressin(2)-B. Furthermore, Ucn III stimulated glucagon and insulin release from isolated rat islets, and astressin(2)-B abolished the effects of Ucn III, in keeping with a CRFR2-mediated mechanism. Taken together, the present studies suggest pancreatic Ucn III acting through CRFR2 is involved in the local regulation of glucagon and insulin secretion.

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“…Several GLP-1 analogs with greater proteolytic stability and extended plasma half-lives are in clinical development [6]. Recombinant GLP-1 (7-36) amide is identical in structure to the major endogenous GLP-1 species [7], but because of its short half-life, the peptide requires an effective mode of administration. One possibility is CSCI; another may be administration by s. c. injection after the last meal in the evening to control overnight fasting hyperglycemia.…”

Section: Discussionmentioning

confidence: 99%

“…GLP-1 is a peptide hormone secreted by L-cells within the intestinal mucosa in response to food intake. Together with GIP (glucose-dependent insulinotropic polypeptide), GLP-1 is responsible for the incretin effect, the augmentation of glucose-stimulated insulin secretion after ingestion of a meal [7]. In addition to its well-documented, glucose-dependent insulinotropic and glucagonostatic effects, GLP-1 also inhibits gastric emptying and reduces appetite and food intake.…”

Section: Introductionmentioning

confidence: 99%

Recombinant Glucagon-like Peptide-1 (7-36 amide) Lowers Fasting Serum Glucose in a Broad Spectrum of Patients with Type 2 Diabetes

Ehlers¹,

Klaff²,

D’Alessio³

et al. 2003

Horm Metab Res

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Glucagon and Glucagon‐like Peptide Production and Degradation

Abstract: The sections in this article are: History Glucagon Glucagon‐like Peptides The Glucagon Superfamily of Peptide Hormones Tissue Distribution of Proglucagon Expression Pancreas Intestine Brain … Show more

Cited by 4 publications

References 893 publications

Alterations in circadian and meal-induced gut peptide levels in lean and obese rats

Alterations in circadian and meal-induced gut peptide levels in lean and obese rats

Urocortin III Is Expressed in Pancreatic β-Cells and Stimulates Insulin and Glucagon Secretion

Recombinant Glucagon-like Peptide-1 (7-36 amide) Lowers Fasting Serum Glucose in a Broad Spectrum of Patients with Type 2 Diabetes

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