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Nutrient absorption
Shadab A. Siddiqi1, N. Suresh Kumar, David F. Nutting
1Department of Medicine, Division of Gastroenterology and Department of Physiology, The University of Tennessee Health Science Center, Memphis, Tennessee, USA.
Abstract:
Some interesting advances in mechanisms and regulation of nutrient absorption were reported last year. Further evidence was obtained that the rate-limiting step in triacylglycerol absorption, especially with large doses of lipid, is transport of prechylomicrons from the endoplasmic reticulum to the Golgi apparatus. Targeted disruption of the adenosine triphosphate-binding cassette transporter in mice produced changes similar to human Tangier disease and suggested that this mouse may be a model for studying intestinal high-density lipoprotein assembly and secretion. A new mechanism for carbohydrate malabsorption was discovered: in sucrase-isomaltase deficiency, the enzyme fails to anchor in the brush border membrane and so is secreted into the lumen, where it is ineffective. Glycosylating insulin at B1 phenylalanine permitted it to bind to the brush border membrane and greatly enhanced its hypoglycemic activity when given orally. CaCo-2 cells and normal human enterocytes were shown to have two variants of the human sodium-dependent vitamin C transporter, hSVCT1; one is active and the other is an inactive splice variant. In rats, the divalent metal ion transporter, DMT1, appeared to be important for regulation of both absorption of iron and its movement into the liver.
Insights
Nutrient absorption mechanisms advanced, revealing lipid transport rate limits and carbohydrate malabsorption causes. Research also explored vitamin C transporters and iron regulation by DMT1.
Area of Science:
- Gastroenterology and Nutrition Science
- Molecular and Cellular Biology
- Biochemistry
Background:
- Nutrient absorption is crucial for health, with complex regulatory mechanisms.
- Understanding these processes is key to addressing malabsorption disorders and metabolic diseases.
Purpose of the Study:
- To elucidate novel mechanisms and regulatory pathways in nutrient absorption.
- To investigate the roles of specific transporters and enzymes in intestinal nutrient handling.
Main Methods:
- Utilized mouse models with targeted gene disruption (adenosine triphosphate-binding cassette transporter).
- Employed cell culture (CaCo-2 cells) and human enterocyte studies.
- Investigated enzyme function in sucrase-isomaltase deficiency and modified insulin for oral delivery.
Main Results:
- Identified prechylomicron transport as a rate-limiting step in triacylglycerol absorption.
- Demonstrated a mouse model for Tangier disease and intestinal high-density lipoprotein assembly.
- Discovered carbohydrate malabsorption due to enzyme secretion in sucrase-isomaltase deficiency.
- Showcased enhanced oral hypoglycemic activity of glycosylated insulin.
- Characterized active and inactive variants of the human sodium-dependent vitamin C transporter (hSVCT1).
- Highlighted the role of divalent metal ion transporter 1 (DMT1) in iron absorption and hepatic transport in rats.
Conclusions:
- Significant advances were made in understanding nutrient absorption regulation.
- New insights into lipid, carbohydrate, vitamin C, and iron absorption mechanisms were gained.
- These findings provide a basis for future therapeutic strategies for malabsorption and metabolic disorders.