Simultaneous Measurement of the Pancreatic and Biliary Response to CCk and Secretin

Gardiner, Barry N.; Small, Donald

doi:10.1016/s0016-5085(76)80154-0

Cited by 9 publications

(2 citation statements)

References 7 publications

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“…Its action in the gastrointestinal system aids fat digestion and absorption, and therefore leads to an increase in cholesterol uptake via chylomicrons [4]. Specifically, CCK stimulates the secretion of pancreatic amylases, proteases and lipases.…”

Section: Introductionmentioning

confidence: 99%

“…Several pancreatic lipases are able to hydrolyze cholesterol esters [5], and the resulting free cholesterol and fatty acids are taken up by enterocytes. In addition, CCK stimulates the release of bile into the small intestine [4]. Bile salts form amphipathic micelles that emulsify fats to allow lipases to access lipid molecules (such as cholesterol esters), aiding in their digestion.…”

Section: Introductionmentioning

confidence: 99%

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Cholecystokinin Elevates Mouse Plasma Lipids

et al. 2012

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Cholecystokinin (CCK) is a peptide hormone that induces bile release into the intestinal lumen which in turn aids in fat digestion and absorption in the intestine. While excretion of bile acids and cholesterol into the feces eliminates cholesterol from the body, this report examined the effect of CCK on increasing plasma cholesterol and triglycerides in mice. Our data demonstrated that intravenous injection of [Thr28, Nle31]-CCK at a dose of 50 ng/kg significantly increased plasma triglyceride and cholesterol levels by 22 and 31%, respectively, in fasting low-density lipoprotein receptor knockout (LDLR−/−) mice. The same dose of [Thr28, Nle31]-CCK induced 6 and 13% increases in plasma triglyceride and cholesterol, respectively, in wild-type mice. However, these particular before and after CCK treatment values did not achieve statistical significance. Oral feeding of olive oil further elevated plasma triglycerides, but did not alter plasma cholesterol levels in CCK-treated mice. The increased plasma cholesterol in CCK-treated mice was distributed in very-low, low and high density lipoproteins (VLDL, LDL and HDL) with less of an increase in HDL. Correspondingly, the plasma apolipoprotein (apo) B48, B100, apoE and apoAI levels were significantly higher in the CCK-treated mice than in untreated control mice. Ligation of the bile duct, blocking CCK receptors with proglumide or inhibition of Niemann-Pick C1 Like 1 transporter with ezetimibe reduced the hypercholesterolemic effect of [Thr28, Nle31]-CCK in LDLR−/− mice. These findings suggest that CCK-increased plasma cholesterol and triglycerides as a result of the reabsorption of biliary lipids from the intestine.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cholecystokinin Elevates Mouse Plasma Lipids

et al. 2012

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Pancreatic Secretion of Electrolytes and Water

Case

Argent

1989

Comprehensive Physiology

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Animal Farm: Considerations in Animal Gastrointestinal Physiology and Relevance to Drug Delivery in Humans

Hatton

Yadav

Basit

et al. 2015

Journal of Pharmaceutical Sciences

165

120

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"All animals are equal, but some are more equal than others" was the illustrious quote derived from British writer George Orwell's famed work, Animal Farm. Extending beyond the remit of political allegory, however, this statement would appear to hold true for the selection of appropriate animal models to simulate human physiology in preclinical studies. There remain definite gaps in our current knowledge with respect to animal physiology, notably those of intra- and inter-species differences in gastrointestinal (GI) function, which may affect oral drug delivery and absorption. Factors such as cost and availability have often influenced the choice of animal species without clear justification for their similarity to humans, and lack of standardization in techniques employed in past studies using various animals may also have contributed to the generation of contradictory results. As it stands, attempts to identify a single animal species as appropriately representative of human physiology and which may able to adequately simulate human in vivo conditions are limited. In this review, we have compiled and critically reviewed data from numerous studies of GI anatomy and physiology of various animal species commonly used in drug delivery modeling, commenting on the appropriateness of these animals for in vivo comparison and extrapolation to humans.

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Simultaneous Measurement of the Pancreatic and Biliary Response to CCk and Secretin

Cited by 9 publications

References 7 publications

Cholecystokinin Elevates Mouse Plasma Lipids

Cholecystokinin Elevates Mouse Plasma Lipids

Pancreatic Secretion of Electrolytes and Water

Animal Farm: Considerations in Animal Gastrointestinal Physiology and Relevance to Drug Delivery in Humans

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