Diabetes-induced mechanophysiological changes in the small intestine and colon

Table 1 Biomechanical properties of normal small intestine and colon

	Biomechanical properties
Intestine	Tension-strain or stress-strain curves show an exponential behavior[19-23]
	The stiffness differs between the duodenal, jejunal and ileal segments[20,21,24]
	All segments are stiffest in longitudinal direction[20,21,24]
	The opening angle and residual strain shows a large axial variation[25]. The axial variation correlates to the morphometric variation[26]
	The serosal residual strains are tensile and the mucosal residual strains are compressive[24,25,27]
	The residual strains in longitudinal direction are smaller than those in circumferential direction[24], especially on the mucosal side
	The opening angle changes over time for all the small intestine segments. The viscoelastic constant of the rat small intestine is fairly homogenous along its length[28]
	The collagen in submucosa layer is important for the passive biomechanical properties[29,30]
	The villi are important for the biomechanical properties of the small intestine in circumferential direction[31]
Colon	The rat colon has a tensile strength of around 50 g/mm2 and increases in strength from proximal to distal[33]
	Quasi-static P-V curves in colon are approximated to a power exponential function and revealed hysteresis, indicative of viscoelasticity[34]
	The opening angle vary along the rat colon with the highest values in the beginning of the proximal colon[35]. The residual strain is negative at the inner surface and positive at the outer surface[35]
	The stress-strain curves are exponential. All segments were stiffer in longitudinal direction than in the circumferential direction[35]
	In human sigmoid colon, the spatial distributions of the biomechanical parameters are non-homogeneous. The circumferential length, strain, pressure and wall stress increase as a function of bag volume[36]
	The wall stiffness of human sigmoid colon is reduced in response to butylscopolamine[36]
	The phasic and tonic responses to the meal in two colonic regions of human are quantitatively different but qualitatively similar[37]
	Smooth muscle cells in the gastrointestinal tract are constantly being deformed due to forces generated by the muscle cells themselves or by the surroundings[38,39]
	A mechanical creep behavior in the isolated rat colon smooth muscle cells could be described by a viscoelastic solid model[40]

Table 2 Diabetes mellitus-induced histomorphological changes of intestine and colon

	Intestine	Colon
Mucosa	Increased thickness[5,8,47,49]; Damaged tight junctions[260]; Proliferation of villi and crypt[41]; Decreased membrane fluidity[110]; Enhanced transport of glucose, amino acid, bile salts, phosphate, fatty acids, fatty alcohols, and cholesterol[110]; Decreased protein synthesis[261]; Increased expression of the monosaccharide transporters[262,263]; Increased expression of AGE and RAGE[47,49]	Increased thickness[10,49]; Increased thickness of the subepithelial collagen layer[276,277]; Abnormalities of endocrine cells[278]; Increased expression of RAGE[49]; Increased expression of AGE, RAGE, TGF-β1 and TGF-β1 receptor[52]
Submucosa	Increased thickness[5,8,47]	Increased thickness[10]; Increased expression of AGE, RAGE, TGF-β1 and TGF-β1 receptor[52]
Muscle	Increased thickness[8,47]; Increased expression of AGE and RAGE[49]	Increased thickness[10]; Hypertrophy of smooth muscle cells[51]; Increase type I collagen and expression of AGE[51]; Increased expression of AGE, RAGE, TGF-β1 and TGF-β1 receptor[52]
Wall as a whole	Increased thickness[8,47-50]; Increase expression of substance P[264] and neuronal nitric oxide synthase[265]; Dcreased expression of substance P[266], vasoactive intestinal polypeptide[262] and neuronal nitric oxide synthase[267]; Increased RAGE mRNA level[50]	Increased thickness[10,49]; Increase in substance P levels[264]
Nerve and ICC	Nuroaxonal dystrophy[48,268]; Decreased myenteric ganglia[269]; Decreased nitrergic neuronal cell number[270]; Decreased density of myenteric neurons[120]; Decreased number of myenteric neurons[271,272]; Increased expression of RAGE[49]; Decreased myosin-V-immunoreactive neurons[273]; Decreased ghrelin cell density[274]; Reduced number of ICC[99,275]	Impairment of nitrergic enteric neurons[111]; Decrease density and size of the myenteric neurons[15]; Decreased nitrergic neuronal cell number[280]; Decreased the numbers of nNOS, CHAT neurons and total neurons[279]; Increased expression of RAGE[49]; Apoptosis of neurons[244]; Decreased ghrelin cell density[274]; Reduced number of ICC[99,110,124,280] and impairment in the ultrastructures of ICC[99]

AGE: Advanced glycation end of product; RAGE: Advanced glycation end of product receptor; ICC: Interstitial cells of Cajal.

Table 3 Diabetes mellitus-induced motor and sensory changes of intestine and colon

Changes	Intestine	Colon
Motor	Transit time ↑↓[43,78-80,84,87] Muscle tone ↓[80] Jejunal contractility in response to flow and ramp distension after carbachol application ↑[81] Ileal contractility in response to distension ↑[83] The force generated by the smooth muscle per unit ↓[82,83] Dysmotility DM patients[88,90] Migrating motor complex disorders[89]	Transit time ↑[85,92-99,101,102,106] Contractility ↑↓[104,108,109,111-113] Carbachol induced contractions in muscle ↑↓[100,107,112] Spontaneous contractility ↑↓[100,102] Contraction and relaxation of circular muscle strips from DM were impaired[105]
Sensory	Sensitivity of human duodenum to the combination of mechanical, thermal and electrical stimulations ↓[114] Sensitivity of rat jejunum to the mechanical stimulation ↑	Sensitivity of rat colon to the mechanical stimulation ↑[103,115,116]

DM: Diabetes mellitus.