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GIP and GLP-1, the two incretin hormones: Similarities and differences.

Seino Y, Fukushima M, Yabe D - J Diabetes Investig (2010)

Bottom Line: GIP and GLP-1 exert their effects by binding to their specific receptors, the GIP receptor (GIPR) and the GLP-1 receptor (GLP-1R), which belong to the G-protein coupled receptor family.In addition to their insulinotropic effects, GIP and GLP-1 play critical roles in various biological processes in different tissues and organs that express GIPR and GLP-1R, including the pancreas, fat, bone and the brain.In the brain, both GIP and GLP-1 are thought to be involved in memory formation as well as the control of appetite.

View Article: PubMed Central - PubMed

Affiliation: The Division of Diabetes, Clinical Nutrition and Endocrinology, Kansai Electric Power Hospital, Osaka.

ABSTRACT
Gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the two primary incretin hormones secreted from the intestine on ingestion of glucose or nutrients to stimulate insulin secretion from pancreatic β cells. GIP and GLP-1 exert their effects by binding to their specific receptors, the GIP receptor (GIPR) and the GLP-1 receptor (GLP-1R), which belong to the G-protein coupled receptor family. Receptor binding activates and increases the level of intracellular cyclic adenosine monophosphate in pancreatic β cells, thereby stimulating insulin secretion glucose-dependently. In addition to their insulinotropic effects, GIP and GLP-1 play critical roles in various biological processes in different tissues and organs that express GIPR and GLP-1R, including the pancreas, fat, bone and the brain. Within the pancreas, GIP and GLP-1 together promote β cell proliferation and inhibit apoptosis, thereby expanding pancreatic β cell mass, while GIP enhances postprandial glucagon response and GLP-1 suppresses it. In adipose tissues, GIP but not GLP-1 facilitates fat deposition. In bone, GIP promotes bone formation while GLP-1 inhibits bone absorption. In the brain, both GIP and GLP-1 are thought to be involved in memory formation as well as the control of appetite. In addition to these differences, secretion of GIP and GLP-1 and their insulinotropic effects on β cells have been shown to differ in patients with type 2 diabetes compared to healthy subjects. We summarize here the similarities and differences of these two incretin hormones in secretion and metabolism, their insulinotropic action on pancreatic β cells, and their non-insulinotropic effects, and discuss their potential in treatment of type 2 diabetes. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00022.x, 2010).

No MeSH data available.


Related in: MedlinePlus

 Racial differences in secretion and metabolism of (a) glucose‐dependent insulinotropic polypepide (GIP) and (b) glucagon‐like peptide (GLP)‐1. GIP secretion in healthy Japanese subjects after ingestion of glucose or mixed meals were higher than those of healthy Caucasian subjects, whereas levels of intact GIP were similar37,40–42. This suggests processing of GIP by dipeptidyl peptidase‐4 (DPP‐4) in Japanese subjects might be enhanced. Considerably low levels of intact GLP‐1 after ingestion of glucose or mixed meals are also consistent with enhanced DPP‐4 activities in Japanese subjects. To compare early phase incretin secretion and their processing by DPP‐4 between non‐obese (BMI <25) healthy Japanese and Caucasian subjects, area under the curves during 0–30 min after ingestion of mixed meals containing similar calories are plotted for total and intact forms of (a) GIP and (b) GLP‐1 from Yabe et al.42 Note that total and intact GIP and total GLP‐1 levels were measured in the same immunoassays, whereas assays for intact GLP‐1 were similar except for the presence or absence of the ethanol extraction.
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f4:  Racial differences in secretion and metabolism of (a) glucose‐dependent insulinotropic polypepide (GIP) and (b) glucagon‐like peptide (GLP)‐1. GIP secretion in healthy Japanese subjects after ingestion of glucose or mixed meals were higher than those of healthy Caucasian subjects, whereas levels of intact GIP were similar37,40–42. This suggests processing of GIP by dipeptidyl peptidase‐4 (DPP‐4) in Japanese subjects might be enhanced. Considerably low levels of intact GLP‐1 after ingestion of glucose or mixed meals are also consistent with enhanced DPP‐4 activities in Japanese subjects. To compare early phase incretin secretion and their processing by DPP‐4 between non‐obese (BMI <25) healthy Japanese and Caucasian subjects, area under the curves during 0–30 min after ingestion of mixed meals containing similar calories are plotted for total and intact forms of (a) GIP and (b) GLP‐1 from Yabe et al.42 Note that total and intact GIP and total GLP‐1 levels were measured in the same immunoassays, whereas assays for intact GLP‐1 were similar except for the presence or absence of the ethanol extraction.

Mentions: GIP secretion from K cells is enhanced in response to ingestion of meals or glucose36. A series of studies using the antibody R65, which recognizes both intact GIP(1–42) and DPP‐4‐processed GIP(3–42), shows that plasma levels of total GIP at fasting are 5–20 pM in healthy Caucasians36, indicating basal secretion in healthy Caucasians. These levels of total GIP reach 50–100 pM within 30 min in response to ingestion of 75‐gram glucose in healthy Caucasians, whereas those of total GIP reach 100–150 pM within 60 min in response to ingestion of mixed meals36,37. Although there is no direct comparison of glucose‐enhanced GIP secretion with those enhanced by proteins or fats, ingestion of proteins produces more rapid and robust GIP secretion than that of fats38. Similarly, levels of intact GIP, determined by an immunoassay using antiserum 98171, which detects GIP(1–42) but not GIP(3–42)39, increase more rapidly and robustly in response to ingestion of proteins when compared with isocaloric fat ingestion38. These results suggest that the GIP response is dependent not only on meal size but also on meal composition. Recent investigations of GIP secretion in healthy Japanese subjects using the same immunoassays showed that although peak values of total GIP levels in response to ingestion of glucose or mixed meals are higher than those of Caucasians, the peak values of intact GIP levels are similar37,40–42, suggesting enhanced processing of GIP by DPP‐4 in Japanese subjects (Figure 4). This possible racial difference in the GIP response and DPP‐4 activities needs to be studied more intensively in the future.


GIP and GLP-1, the two incretin hormones: Similarities and differences.

Seino Y, Fukushima M, Yabe D - J Diabetes Investig (2010)

 Racial differences in secretion and metabolism of (a) glucose‐dependent insulinotropic polypepide (GIP) and (b) glucagon‐like peptide (GLP)‐1. GIP secretion in healthy Japanese subjects after ingestion of glucose or mixed meals were higher than those of healthy Caucasian subjects, whereas levels of intact GIP were similar37,40–42. This suggests processing of GIP by dipeptidyl peptidase‐4 (DPP‐4) in Japanese subjects might be enhanced. Considerably low levels of intact GLP‐1 after ingestion of glucose or mixed meals are also consistent with enhanced DPP‐4 activities in Japanese subjects. To compare early phase incretin secretion and their processing by DPP‐4 between non‐obese (BMI <25) healthy Japanese and Caucasian subjects, area under the curves during 0–30 min after ingestion of mixed meals containing similar calories are plotted for total and intact forms of (a) GIP and (b) GLP‐1 from Yabe et al.42 Note that total and intact GIP and total GLP‐1 levels were measured in the same immunoassays, whereas assays for intact GLP‐1 were similar except for the presence or absence of the ethanol extraction.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4020673&req=5

f4:  Racial differences in secretion and metabolism of (a) glucose‐dependent insulinotropic polypepide (GIP) and (b) glucagon‐like peptide (GLP)‐1. GIP secretion in healthy Japanese subjects after ingestion of glucose or mixed meals were higher than those of healthy Caucasian subjects, whereas levels of intact GIP were similar37,40–42. This suggests processing of GIP by dipeptidyl peptidase‐4 (DPP‐4) in Japanese subjects might be enhanced. Considerably low levels of intact GLP‐1 after ingestion of glucose or mixed meals are also consistent with enhanced DPP‐4 activities in Japanese subjects. To compare early phase incretin secretion and their processing by DPP‐4 between non‐obese (BMI <25) healthy Japanese and Caucasian subjects, area under the curves during 0–30 min after ingestion of mixed meals containing similar calories are plotted for total and intact forms of (a) GIP and (b) GLP‐1 from Yabe et al.42 Note that total and intact GIP and total GLP‐1 levels were measured in the same immunoassays, whereas assays for intact GLP‐1 were similar except for the presence or absence of the ethanol extraction.
Mentions: GIP secretion from K cells is enhanced in response to ingestion of meals or glucose36. A series of studies using the antibody R65, which recognizes both intact GIP(1–42) and DPP‐4‐processed GIP(3–42), shows that plasma levels of total GIP at fasting are 5–20 pM in healthy Caucasians36, indicating basal secretion in healthy Caucasians. These levels of total GIP reach 50–100 pM within 30 min in response to ingestion of 75‐gram glucose in healthy Caucasians, whereas those of total GIP reach 100–150 pM within 60 min in response to ingestion of mixed meals36,37. Although there is no direct comparison of glucose‐enhanced GIP secretion with those enhanced by proteins or fats, ingestion of proteins produces more rapid and robust GIP secretion than that of fats38. Similarly, levels of intact GIP, determined by an immunoassay using antiserum 98171, which detects GIP(1–42) but not GIP(3–42)39, increase more rapidly and robustly in response to ingestion of proteins when compared with isocaloric fat ingestion38. These results suggest that the GIP response is dependent not only on meal size but also on meal composition. Recent investigations of GIP secretion in healthy Japanese subjects using the same immunoassays showed that although peak values of total GIP levels in response to ingestion of glucose or mixed meals are higher than those of Caucasians, the peak values of intact GIP levels are similar37,40–42, suggesting enhanced processing of GIP by DPP‐4 in Japanese subjects (Figure 4). This possible racial difference in the GIP response and DPP‐4 activities needs to be studied more intensively in the future.

Bottom Line: GIP and GLP-1 exert their effects by binding to their specific receptors, the GIP receptor (GIPR) and the GLP-1 receptor (GLP-1R), which belong to the G-protein coupled receptor family.In addition to their insulinotropic effects, GIP and GLP-1 play critical roles in various biological processes in different tissues and organs that express GIPR and GLP-1R, including the pancreas, fat, bone and the brain.In the brain, both GIP and GLP-1 are thought to be involved in memory formation as well as the control of appetite.

View Article: PubMed Central - PubMed

Affiliation: The Division of Diabetes, Clinical Nutrition and Endocrinology, Kansai Electric Power Hospital, Osaka.

ABSTRACT
Gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the two primary incretin hormones secreted from the intestine on ingestion of glucose or nutrients to stimulate insulin secretion from pancreatic β cells. GIP and GLP-1 exert their effects by binding to their specific receptors, the GIP receptor (GIPR) and the GLP-1 receptor (GLP-1R), which belong to the G-protein coupled receptor family. Receptor binding activates and increases the level of intracellular cyclic adenosine monophosphate in pancreatic β cells, thereby stimulating insulin secretion glucose-dependently. In addition to their insulinotropic effects, GIP and GLP-1 play critical roles in various biological processes in different tissues and organs that express GIPR and GLP-1R, including the pancreas, fat, bone and the brain. Within the pancreas, GIP and GLP-1 together promote β cell proliferation and inhibit apoptosis, thereby expanding pancreatic β cell mass, while GIP enhances postprandial glucagon response and GLP-1 suppresses it. In adipose tissues, GIP but not GLP-1 facilitates fat deposition. In bone, GIP promotes bone formation while GLP-1 inhibits bone absorption. In the brain, both GIP and GLP-1 are thought to be involved in memory formation as well as the control of appetite. In addition to these differences, secretion of GIP and GLP-1 and their insulinotropic effects on β cells have been shown to differ in patients with type 2 diabetes compared to healthy subjects. We summarize here the similarities and differences of these two incretin hormones in secretion and metabolism, their insulinotropic action on pancreatic β cells, and their non-insulinotropic effects, and discuss their potential in treatment of type 2 diabetes. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00022.x, 2010).

No MeSH data available.


Related in: MedlinePlus