title: Remodeling of the rat distal colon in diabetes: function and ultrastructure.
abstract: This study seeks to define and explain remodeling of the distal colon in the streptozotocin (STZ)-treated rat model of diabetes through analysis of resting and active length dependence of force production, chemical composition, and ultrastructure. Compared with untreated controls, the passive stiffness on extension of the diabetic muscle is high, and active force produced at short muscle lengths is amplified but is limited by an internal resistance to shortening. The latter are accounted for by a significant increase in collagen type 1, with no changes in types 3 and 4. In the diabetic colon, ultrastructural studies show unique, conspicuous pockets of collagen among muscle cells, in addition to a thickened basement membrane and an extracellular space filled with collagen fibers and various fibrils. Measurements of DNA and total protein content revealed that the diabetic colon underwent hypertrophy, along with a proportional increase in actin and myosin contents, with no change in the actin-to-myosin ratio. Active force production per cross-sectional area was not different in the diabetic and normal muscles, consistent with the proportionality of changes in contractile proteins. The stiffness and the limit to shortening of the diabetic colon were significantly reduced by treatment with the glycation breaker alagebrium chloride (ALT-711), with no change in collagen contents. Functionally, this study shows that, in diabetes, the production of collagen type 1 and glycation increase stiffness, which limits distensibility on filling and limits shortening and expulsion of contents, both of which can be alleviated by treatment with ALT-711.
authors.affiliation: Department of Molecular Physiology and Biophysics, Sidney Kimmel College of Medicine at Thomas Jefferson University, Philadelphia, Pennsylvania marion.siegman@jefferson.edu.
authors.forename: Marion J
authors.initials: MJ
authors.lastname: Siegman
authors.affiliation: Department of Molecular Physiology and Biophysics, Sidney Kimmel College of Medicine at Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Masumi
authors.initials: M
authors.lastname: Eto
authors.affiliation: Department of Molecular Physiology and Biophysics, Sidney Kimmel College of Medicine at Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Butler
mesh_terms: D000818:Animals; D024042:Collagen Type I / Q000378:metabolism*; D003106:Colon / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure*; D003921:Diabetes Mellitus, Experimental / Q000473:pathology* / Q000503:physiopathology*; D055119:Elastic Modulus; D017127:Glycation End Products, Advanced / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D014018:Tissue Distribution
chemical_list: D024042:Collagen Type I; D017127:Glycation End Products, Advanced
keywords: actin; advanced glycation end products; collagen; extracellular matrix; hypertrophy; myosin