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Research Project: Pediatric Clinical Nutrition

Location: Children's Nutrition Research Center

Title: Starch source influences dietary glucose generation at the mucosal alpha-glucosidase level

item LIN, AMY HUI-MEI - Purdue University
item LEE, BYUNG-HOO - Purdue University
item NICHOLS, BUFORD - Children'S Nutrition Research Center (CNRC)
item QUEZADA-CALVILLO, ROBERTO - Children'S Nutrition Research Center (CNRC)
item ROSE, DAVID - University Of Waterloo
item NAIM, HASSAN - Hannover School Of Veterinary Medicine
item HAMAKER, BRUCE - Purdue University

Submitted to: Journal of Biological Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/12/2012
Publication Date: 9/17/2012
Citation: Lin, A., Lee, B., Nichols, B.L., Quezada-Calvillo, R., Rose, D.R., Naim, H.Y., Hamaker, B.R. 2012. Starch source influences dietary glucose generation at the mucosal alpha-glucosidase level. Journal of Biological Chemistry. 287(44):36917-36921.

Interpretive Summary: Starch digestion is associated with blood glucose-related problems, such as type 2 diabetes or pre-diabetes. We found that the rate of glucose generation from dietary starch in the gut is associated with enzymes located on cells lining the gut (known as mucosal enzymes), and not just with enzymes released into the gut from the pancreas. Starches are normally digested extensively by pancreatic enzymes. We identified specific roles of the individual mucosal enzymes for breakdown products that persist after starches are first broken down by pancreatic enzymes. We used mucosal enzymes to test starches from different corn varieties and were able to show that not all starches were digested equally. These results revealed that the source of food starch influences glucose generation. In addition, a small portion of starch breakdown products were discovered that were resistant to the extensive digestion by all the mucosal and pancreatic enzymes. These findings tell us that by feeding slowly digestible food starches, the rate of glucose production could be controlled in the gut. This strategy could lead to the regulation of meal related blood glucose responses in normal populations and could result in improved ways to manage type 2 diabetes or pre-diabetes.

Technical Abstract: The quality of starch digestion, related to the rate and extent of release of dietary glucose, is associated with glycemia-related problems such as diabetes and other metabolic syndrome conditions. Here, we found that the rate of glucose generation from starch is unexpectedly associated with mucosal alpha-glucosidases and not just alpha-amylase. This understanding could lead to a new approach to regulate the glycemic response and glucose-related physiologic responses in the human body. There are six digestive enzymes for starch: salivary and pancreatic alpha-amylases and four mucosal alpha-glucosidases, including N- and C-terminal subunits of both maltase-glucoamylase and sucrase-isomaltase. Only the mucosal alpha-glucosidases provide the final hydrolytic activities to produce substantial free glucose. We report here the unique and shared roles of the individual alpha-glucosidases for alpha-glucans persisting after starch is extensively hydrolyzed by alpha-amylase (to produce alpha-limit dextrins (alpha-LDx)). All four alpha-glucosidases share digestion of linear regions of alpha-LDx, and three can hydrolyze branched fractions. The alpha-LDx, which were derived from different maize cultivars, were not all equally digested, revealing that the starch source influences glucose generation at the mucosal alpha-glucosidase level. We further discovered a fraction of alpha-LDx that was resistant to the extensive digestion by the mucosal alpha-glucosidases. Our study further challenges the conventional view that alpha-amylase is the only rate-determining enzyme involved in starch digestion and better defines the roles of individual and collective mucosal alpha-glucosidases. Strategies to control the rate of glucogenesis at the mucosal level could lead to regulation of the glycemic response and improved glucose management in the human body.