Comparison of sub-chronic metabolic effects of stable forms of naturally occurring GIP(1-30) and GIP(1-42) in high-fat fed mice

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Abstract

Glucose-dependent insulinotropic polypeptide (GIP) is a 42 amino acid hormone secreted from intestinal K-cells, which exhibits a number of actions including stimulation of insulin release. A truncated form, GIP(1-30), has recently been demonstrated in intestine and islet alpha-cells. To evaluate the potential physiological significance of this naturally occurring form of GIP, the present study has examined and compared the bioactivity of enzymatically stabilised forms, [D-Ala(2)]-GIP(1-30) and [D-Ala(2)]GIP(1-42), in high-fat fed mice. Twice-daily injection of GIP peptides for 42 days had no significant effect on food intake or body weight. However, non-fasting glucose levels were significantly lowered, and insulin levels were elevated in both treatment groups compared to saline controls. The glycaemic response to i.p. glucose was correspondingly improved (P < 0.05) in [D-Ala(2)]GIP(1-30)- and [D-Ala(2)]GIP(1-42)-treated mice. Furthermore, glucose-stimulated plasma insulin levels were significantly elevated in both treatment groups compared to control mice. Insulin sensitivity was not significantly different between any of the groups. Similarly, plasma lipid profile, O-2 consumption, CO2 production, respiratory exchange ratio, and energy expenditure were not altered by 42 days twice-daily treatment with [D-Ala(2)]GIP(1-30) or [D-Ala(2)]GIP(1-42). In contrast, ambulatory activity was significantly (P < 0.05) elevated during the light phase in both GIP treatment groups compared to saline controls. The results reveal that sustained GIP receptor activation exerts a spectrum of beneficial metabolic effects in high-fat fed mice. However, no differences were discernable between the biological actions of the enzyme-resistant analogues of the naturally occurring forms, GIP(1-30) and GIP(1-42). Journal of Endocrinology (2011) 208, 265-271
LanguageEnglish
Pages265-271
JournalJournal of Endrocrinology
Volume208
Issue number3
DOIs
Publication statusPublished - Mar 2011

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Fats
Glucose
Peptides
Insulin
Gastric Inhibitory Polypeptide
Gastrointestinal Hormones
gastric inhibitory polypeptide (1-42)
Endocrinology
Therapeutics
Islets of Langerhans
Energy Metabolism
Intestines
Insulin Resistance
Ala(2)-glucose-dependent insulinotropic polypeptide
Eating
Body Weight
Lipids
Light
Amino Acids
Injections

Cite this

@article{29c856d680c54d658a904fa6a59d1fa3,
title = "Comparison of sub-chronic metabolic effects of stable forms of naturally occurring GIP(1-30) and GIP(1-42) in high-fat fed mice",
abstract = "Glucose-dependent insulinotropic polypeptide (GIP) is a 42 amino acid hormone secreted from intestinal K-cells, which exhibits a number of actions including stimulation of insulin release. A truncated form, GIP(1-30), has recently been demonstrated in intestine and islet alpha-cells. To evaluate the potential physiological significance of this naturally occurring form of GIP, the present study has examined and compared the bioactivity of enzymatically stabilised forms, [D-Ala(2)]-GIP(1-30) and [D-Ala(2)]GIP(1-42), in high-fat fed mice. Twice-daily injection of GIP peptides for 42 days had no significant effect on food intake or body weight. However, non-fasting glucose levels were significantly lowered, and insulin levels were elevated in both treatment groups compared to saline controls. The glycaemic response to i.p. glucose was correspondingly improved (P < 0.05) in [D-Ala(2)]GIP(1-30)- and [D-Ala(2)]GIP(1-42)-treated mice. Furthermore, glucose-stimulated plasma insulin levels were significantly elevated in both treatment groups compared to control mice. Insulin sensitivity was not significantly different between any of the groups. Similarly, plasma lipid profile, O-2 consumption, CO2 production, respiratory exchange ratio, and energy expenditure were not altered by 42 days twice-daily treatment with [D-Ala(2)]GIP(1-30) or [D-Ala(2)]GIP(1-42). In contrast, ambulatory activity was significantly (P < 0.05) elevated during the light phase in both GIP treatment groups compared to saline controls. The results reveal that sustained GIP receptor activation exerts a spectrum of beneficial metabolic effects in high-fat fed mice. However, no differences were discernable between the biological actions of the enzyme-resistant analogues of the naturally occurring forms, GIP(1-30) and GIP(1-42). Journal of Endocrinology (2011) 208, 265-271",
author = "Victor Gault and Porter, {David W.} and Nigel Irwin and Peter Flatt",
year = "2011",
month = "3",
doi = "10.1530/JOE-10-0419",
language = "English",
volume = "208",
pages = "265--271",
journal = "Journal of Endrocrinology",
issn = "0022-0795",
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TY - JOUR

T1 - Comparison of sub-chronic metabolic effects of stable forms of naturally occurring GIP(1-30) and GIP(1-42) in high-fat fed mice

AU - Gault, Victor

AU - Porter, David W.

AU - Irwin, Nigel

AU - Flatt, Peter

PY - 2011/3

Y1 - 2011/3

N2 - Glucose-dependent insulinotropic polypeptide (GIP) is a 42 amino acid hormone secreted from intestinal K-cells, which exhibits a number of actions including stimulation of insulin release. A truncated form, GIP(1-30), has recently been demonstrated in intestine and islet alpha-cells. To evaluate the potential physiological significance of this naturally occurring form of GIP, the present study has examined and compared the bioactivity of enzymatically stabilised forms, [D-Ala(2)]-GIP(1-30) and [D-Ala(2)]GIP(1-42), in high-fat fed mice. Twice-daily injection of GIP peptides for 42 days had no significant effect on food intake or body weight. However, non-fasting glucose levels were significantly lowered, and insulin levels were elevated in both treatment groups compared to saline controls. The glycaemic response to i.p. glucose was correspondingly improved (P < 0.05) in [D-Ala(2)]GIP(1-30)- and [D-Ala(2)]GIP(1-42)-treated mice. Furthermore, glucose-stimulated plasma insulin levels were significantly elevated in both treatment groups compared to control mice. Insulin sensitivity was not significantly different between any of the groups. Similarly, plasma lipid profile, O-2 consumption, CO2 production, respiratory exchange ratio, and energy expenditure were not altered by 42 days twice-daily treatment with [D-Ala(2)]GIP(1-30) or [D-Ala(2)]GIP(1-42). In contrast, ambulatory activity was significantly (P < 0.05) elevated during the light phase in both GIP treatment groups compared to saline controls. The results reveal that sustained GIP receptor activation exerts a spectrum of beneficial metabolic effects in high-fat fed mice. However, no differences were discernable between the biological actions of the enzyme-resistant analogues of the naturally occurring forms, GIP(1-30) and GIP(1-42). Journal of Endocrinology (2011) 208, 265-271

AB - Glucose-dependent insulinotropic polypeptide (GIP) is a 42 amino acid hormone secreted from intestinal K-cells, which exhibits a number of actions including stimulation of insulin release. A truncated form, GIP(1-30), has recently been demonstrated in intestine and islet alpha-cells. To evaluate the potential physiological significance of this naturally occurring form of GIP, the present study has examined and compared the bioactivity of enzymatically stabilised forms, [D-Ala(2)]-GIP(1-30) and [D-Ala(2)]GIP(1-42), in high-fat fed mice. Twice-daily injection of GIP peptides for 42 days had no significant effect on food intake or body weight. However, non-fasting glucose levels were significantly lowered, and insulin levels were elevated in both treatment groups compared to saline controls. The glycaemic response to i.p. glucose was correspondingly improved (P < 0.05) in [D-Ala(2)]GIP(1-30)- and [D-Ala(2)]GIP(1-42)-treated mice. Furthermore, glucose-stimulated plasma insulin levels were significantly elevated in both treatment groups compared to control mice. Insulin sensitivity was not significantly different between any of the groups. Similarly, plasma lipid profile, O-2 consumption, CO2 production, respiratory exchange ratio, and energy expenditure were not altered by 42 days twice-daily treatment with [D-Ala(2)]GIP(1-30) or [D-Ala(2)]GIP(1-42). In contrast, ambulatory activity was significantly (P < 0.05) elevated during the light phase in both GIP treatment groups compared to saline controls. The results reveal that sustained GIP receptor activation exerts a spectrum of beneficial metabolic effects in high-fat fed mice. However, no differences were discernable between the biological actions of the enzyme-resistant analogues of the naturally occurring forms, GIP(1-30) and GIP(1-42). Journal of Endocrinology (2011) 208, 265-271

U2 - 10.1530/JOE-10-0419

DO - 10.1530/JOE-10-0419

M3 - Article

VL - 208

SP - 265

EP - 271

JO - Journal of Endrocrinology

T2 - Journal of Endrocrinology

JF - Journal of Endrocrinology

SN - 0022-0795

IS - 3

ER -