Longitudinal versus radial effects of hydroxypropylmethylcellulose on gastrointestinal glucose absorption in dogs.
Many water soluble fibers have been shown to favorably affect the postprandial glucose profile in humans. Hydroxypropylmethylcellulose (HPMC), a fiber which has been shown to increase glucose tolerance in dogs and noninsulin dependent diabetics, was chosen to study the luminal interactions which mediate this effect. The ability of HPMC to influence upper gastrointestinal (GI) viscosity, transit, and water flux of 5% and 20% glucose solutions was studied in five female dogs fistulated at the proximal duodenum and/or midjejunum. HPMC elevated intraluminal viscosity, with a linear relationship existing between input and luminal viscosity. The ability to modify intraluminal viscosity was greater for isoosmotic (5%) glucose solutions than for hyperosmotic (20%) glucose solutions. HPMC also modified the transit profile of isoosmotic (5%) glucose solutions at midgut by both increasing the lag times before the onset of chyme recovery from 5.5+/-3.1 min to 9-55 min (depending on the viscosity of the administered solution) and decreasing the first-order transit rate constants from 0.115+/-0.07 min-1 to 0.014-0.035 min-1. By contrast, the transit profile of hyperosmotic (20%) glucose solutions was not significantly affected. Net cumulative water flux across the gut wall was not significantly affected in either case by the presence of HPMC. These results, in combination with the amount of glucose recovered from midgut fistula, suggest that following the administration of glucose solutions, HPMC effects on blood glucose levels are mediated by mechanisms which relate to the increased intraluminal viscosity but vary according to the input glucose load. For isoosmotic glucose loads, both the decreased upper GI transit rate and hindered radial movement play a role. Although HPMC modifies glucose absorption from hyperosmotic solutions, this study shows that luminal effects occurring before midgut are modest.
Reppas
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College of Pharmacy, The University of Michigan, Ann Arbor, MI, USA.
Greenwood
D E
DE
Dressman
J B
JB
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004043:Dietary Fiber / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D005772:Gastrointestinal Transit / Q000187:drug effects; D005947:Glucose / Q000737:chemistry / Q000378:metabolism*; D065347:Hypromellose Derivatives; D007408:Intestinal Absorption / Q000187:drug effects*; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000494:pharmacology; D009994:Osmolar Concentration; D012996:Solutions; D014783:Viscosity
D001786:Blood Glucose; D004043:Dietary Fiber; D012996:Solutions; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D005947:Glucose