(pGlu-Gln)-CCK-8[mPEG]: A novel, long-acting, mini-PEGylated cholecystokinin (CCK) agonist that improves metabolic status in dietary-induced diabetes

Irwin, Nigel; Frizelle, Pamela; O’Harte, Finbarr; Flatt, Peter R.

doi:10.1016/j.bbagen.2013.04.004

Cited by 18 publications

(9 citation statements)

References 32 publications

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“…and oral glucose tolerance (18 mmol/kg body weight) tests, as well as an insulin sensitivity (25 U/kg body weight for HFF mice and 50 U/kg body weight for ob/ob mice) test were performed. The doses of glucose and insulin used for metabolic tests are based on our extensive previous experience with both animal models . In addition, the metabolic response to glucagon (25 nmol/kg body weight) on day 11 was also assessed.…”

Section: Methodsmentioning

confidence: 99%

Two novel glucagon receptor antagonists prove effective therapeutic agents in high‐fat‐fed and obese diabetic mice

O’Harte

Franklin

Irwin

2014

Diabetes Obesity Metabolism

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Section: Methodsmentioning

confidence: 99%

Two novel glucagon receptor antagonists prove effective therapeutic agents in high‐fat‐fed and obese diabetic mice

O’Harte

Franklin

Irwin

2014

Diabetes Obesity Metabolism

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“…88 They include N-terminally glycosylated CCK-8 and other N-terminally protected CCK analogues (pGlu-Gln-CCK-8, and Ac-Y*-CCK-8). 85,86,89,90 Of these, the pGlu-Gln-CCK-8 designed and tested by Irwin et al 90 looks particularly promising, not least in combination with GLP-1. 86,91 Also, gastrin alone, or in combination with GLP-1 or relevant growth factors, shows promise in treatments of type 1 diabetic rodents.…”

Section: Gastrin and Cck Analogues For Diabetes Therapymentioning

confidence: 99%

Premises for Cholecystokinin and Gastrin Peptides in Diabetes Therapy

Rehfeld

2019

Clin Med Insights Endocrinol Diabetes

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Gastrin and cholecystokinin (CCK) are classical gastrointestinal peptide hormones. Their biogenesis, structures, and intestinal secretory patterns are well-known with the striking feature that their receptor-bound 'active sites' are highly homologous and that this structure is conserved for more than 500 million years during evolution. Consequently, gastrin and CCK are agonists for the same receptor (the CCK 2 receptor). But in addition, tyrosyl O-sulphated CCK are also bound to the specific CCK 1 receptor. The receptors are widely expressed in the body, including pancreatic islet-cell membranes. Moreover, CCK and gastrin peptides are at various developmental stages and diseases expressed in pancreatic islets; also in human islets. Accordingly, bioactive gastrin and CCK peptides stimulate islet-cell growth as well as insulin and glucagon secretion. In view of their insulinotropic effects, gastrin and CCK peptides have come into focus as drug targets, either alone or in combination with other insulinotropic gut hormones or growth factors. So far, modified CCK and gastrin peptides are being examined as potential drugs for therapy of type 1 as well as type 2 diabetes mellitus.

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“…Future investigations should examine if intermittent or pulsatile delivery [83,[196][197][198][199][200][201] of OT will extend its effectiveness and circumvent reductions in OTR binding known to occur in the CNS following chronic CNS infusions [170,171]. In addition, studies should examine if inhibition of oxytocinase activity [64], PEGylation [202][203][204] or conjugation to albumin [205] in combination with oral delivery [206] will produce prolonged effects and eliminate the need for multiple injections.…”

Section: Translational Potentialmentioning

confidence: 99%

Translational and therapeutic potential of oxytocin as an anti-obesity strategy: Insights from rodents, nonhuman primates and humans

Blevins

Baskin

2015

Physiology & Behavior

120

100

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The fact that more than 78 million adults in the US are considered overweight or obese highlights the need to develop new, effective strategies to treat obesity and its associated complications, including type 2 diabetes, kidney disease and cardiovascular disease. While the neurohypophyseal peptide oxytocin (OT) is well recognized for its peripheral effects to stimulate uterine contraction during parturition and milk ejection during lactation, release of OT within the brain is implicated in prosocial behaviors and in the regulation of energy balance. Previous findings indicate that chronic administration of OT decreases food intake and weight gain or elicits weight loss in diet-induced obese (DIO) mice and rats. Furthermore, chronic systemic treatment with OT largely reproduces the effects of central administration to reduce weight gain in DIO and genetically obese rodents at doses that do not appear to result in tolerance. These findings have now been recently extended to more translational models of obesity showing that chronic subcutaneous or intranasal OT treatment is sufficient to elicit body weight loss in DIO nonhuman primates and pre-diabetic obese humans. This review assesses the potential use of OT as a therapeutic strategy for treatment of obesity in rodents, nonhuman primates, and humans, and identifies potential mechanisms that mediate this effect.

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(pGlu-Gln)-CCK-8[mPEG]: A novel, long-acting, mini-PEGylated cholecystokinin (CCK) agonist that improves metabolic status in dietary-induced diabetes

Cited by 18 publications

References 32 publications

Two novel glucagon receptor antagonists prove effective therapeutic agents in high‐fat‐fed and obese diabetic mice

Two novel glucagon receptor antagonists prove effective therapeutic agents in high‐fat‐fed and obese diabetic mice

Premises for Cholecystokinin and Gastrin Peptides in Diabetes Therapy

Translational and therapeutic potential of oxytocin as an anti-obesity strategy: Insights from rodents, nonhuman primates and humans

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