Reduced gastric acid inhibitory effect of a pGIP(1–30)NH2 fragment with potent pancreatic amylase inhibitory activity

Rossowski, W; Zacharia, Susan; Mungan, Zeynel; Özmen, Vahit; Ertan, Atilla; Baylor, Lisa M.; Jiang, Ning; Coy, David H.

doi:10.1016/0167-0115(92)90003-d

Cited by 21 publications

(10 citation statements)

References 13 publications

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“…In 1981 McIntosh et al (26) suggested that gastric somatostatin might mediate the acid-inhibitory action of GIP following their observation that GIP 1-42 potently stimulated somatostatin release from the perfused rat stomach. Subsequent studies also documented that GIP can increase the release of somatostatin in this model (31,36). Here we found that amidated GIP 1-30 is equipotent to GIP in inducing release of gastric somatostatin in mice.…”

Section: Discussionsupporting

confidence: 49%

Differential processing of pro-glucose-dependent insulinotropic polypeptide in gut

Fujita

Asadi

Yang

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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Glucose-dependent insulinotropic polypeptide (GIP) is a hormone released from enteroendocrine K cells in response to meals. Posttranslational processing of the precursor protein pro-GIP at residue 65 by proprotein convertase subtilisin/kexin type 1 (PC1/3) in gut K cells gives rise to the established 42-amino-acid form of GIP (GIP1–42). However, the pro-GIP peptide sequence contains a consensus cleavage site for PC2 at residues 52–55 and we identified PC2 immunoreactivity in a subset of K cells, suggesting the potential existence of a COOH-terminal truncated GIP isoform, GIP1–30. Indeed a subset of mouse and human K cells display GIP immunoreactivity with GIP antibodies directed to the mid portion of the peptide, but not with a COOH-terminal-directed GIP antibody, indicative of the presence of a truncated form of GIP. This population of cells represents ∼5–15% of the total GIP-immunoreactive cells in mice, depending on the region of intestine, and is virtually absent in mice lacking PC2. Amidated GIP1–30 and GIP1–42 have comparable potency at stimulating somatostatin release in the perfused mouse stomach. Therefore, GIP1–30 represents a naturally occurring, biologically active form of GIP.

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Section: Discussionsupporting

confidence: 49%

Differential processing of pro-glucose-dependent insulinotropic polypeptide in gut

Fujita

Asadi

Yang

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…However, details about its elimination are not available-for example, whether immunoreactive metabolites (other than possibly GIP 3-41) circulate. The possibility has been raised that GIP 1-30 amide might be formed as a separate entity (43) and that this peptide might also possess insulinotropic properties. In our previous studies of circulating immunoreactive components using several different antisera (19) we were unable to identlfy components other than the 8and 5-kDa GIP, but the resolution power of the gel filtration technique used then and the assay specificities may have been inadequate to show other molecular forms.…”

Section: Resultsmentioning

confidence: 99%

Secretion of the Incretin Hormones Glucagon-Like Peptide-1 and Gastric Inhibitory Polypeptide Correlates with Insulin Secretion in Normal Man Throughout the Day

Ørskov

Wettergren

Holst

1996

Scandinavian Journal of Gastroenterology

237

140

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“…The high affinity binding region of GIP resides in amino acids 6–30, but the N-terminus has proven critical for actions on the pancreatic islet [12] and, as shown in the current, as well as a previous [33] study, GIP 1–30 and GIP 1–42 exert very similar β-cell effects. However, the C-terminal 12 amino acids have been previously shown to be important for actions on some tissues, as GIP 1–30 exhibited much lower potency than GIP 1–42 for inhibiting gastric acid secretion from the perfused rat stomach [54]. Since, in addition to islets and adipose tissue, GIP also appears to act as a physiological regulator in bone, the gastrointestinal tract, cardiovascular system and brain [12], there may still be tissue specific differences in responses to GIP 1–42 and GIP 1–30 that need to be identified.…”

Section: Discussionmentioning

confidence: 99%

A GIP Receptor Agonist Exhibits β-Cell Anti-Apoptotic Actions in Rat Models of Diabetes Resulting in Improved β-Cell Function and Glycemic Control

et al. 2010

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AimsThe gastrointestinal hormone GIP promotes pancreatic islet function and exerts pro-survival actions on cultured β-cells. However, GIP also promotes lipogenesis, thus potentially restricting its therapeutic use. The current studies evaluated the effects of a truncated GIP analog, D-Ala2-GIP1–30 (D-GIP1–30), on glucose homeostasis and β-cell mass in rat models of diabetes.Materials and MethodsThe insulinotropic and pro-survival potency of D-GIP1–30 was evaluated in perfused pancreas preparations and cultured INS-1 β-cells, respectively, and receptor selectivity evaluated using wild type and GIP receptor knockout mice. Effects of D-GIP1–30 on β-cell function and glucose homeostasis, in vivo, were determined using Lean Zucker rats, obese Vancouver diabetic fatty rats, streptozotocin treated rats, and obese Zucker diabetic fatty rats, with effects on β-cell mass determined in histological studies of pancreatic tissue. Lipogenic effects of D-GIP1–30 were evaluated on cultured 3T3-L1 adipocytes.ResultsAcutely, D-GIP1–30 improved glucose tolerance and insulin secretion. Chronic treatment with D-GIP1–30 reduced levels of islet pro-apoptotic proteins in Vancouver diabetic fatty rats and preserved β-cell mass in streptozotocin treated rats and Zucker diabetic fatty rats, resulting in improved insulin responses and glycemic control in each animal model, with no change in body weight. In in vitro studies, D-GIP1–30 exhibited equivalent potency to GIP1–42 on β-cell function and survival, but greatly reduced action on lipoprotein lipase activity in 3T3-L1 adipocytes.ConclusionsThese findings demonstrate that truncated forms of GIP exhibit potent anti-diabetic actions, without pro-obesity effects, and that the C-terminus contributes to the lipogenic actions of GIP.

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Reduced gastric acid inhibitory effect of a pGIP(1–30)NH2 fragment with potent pancreatic amylase inhibitory activity

Cited by 21 publications

References 13 publications

Differential processing of pro-glucose-dependent insulinotropic polypeptide in gut

Differential processing of pro-glucose-dependent insulinotropic polypeptide in gut

Secretion of the Incretin Hormones Glucagon-Like Peptide-1 and Gastric Inhibitory Polypeptide Correlates with Insulin Secretion in Normal Man Throughout the Day

A GIP Receptor Agonist Exhibits β-Cell Anti-Apoptotic Actions in Rat Models of Diabetes Resulting in Improved β-Cell Function and Glycemic Control

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