Jejunal uptake of sugars, cholesterol, fatty acids, and fatty alcohols in vivo in diabetic rats

1985 ◽  
Vol 63 (11) ◽  
pp. 1356-1361
Author(s):  
C. Hotke ◽  
Y. McIntyre ◽  
A. B. R. Thomson

Previous in vitro studies have demonstrated enhanced active and passive intestinal uptake of nutrients in streptozotocin-diabetic rats, but the effect of diabetes on the in vivo absorption of glucose and amino acids remains controversial, and the effect of diabetes on the in vivo uptake of lipids has not been reported. Accordingly, an in vivo perfusion technique was used in rats to examine the uptake of nutrients from the intestinal lumen, their transfer to the body, their mucosal and submucosal content, and the percentage of uptake transferred. Diabetes was associated with reduced uptake of fatty alcohols, indicating that the effective resistance of the unstirred water layer in vivo is higher in diabetic than in nondiabetic control rats. The mucosal and submucosal content of dodecanol was lower in diabetic than in control rats, but the percentage of the dodecanol uptake transferred to the body was higher. Although the uptake of varying concentrations of D-galactose was similar in diabetic and in control animals, kinetic analysis corrected for unstirred layer effects demonstrated lower mean values of the passive permeability coefficients (Pd) for galactose in diabetic than in control animals, with lower values of the Michaelis constant (Km) and higher values of the maximal transport rate [Formula: see text]. The uptake of lauric acid was reduced in diabetic rats, whereas the uptake of deconoic acid and of cholesterol was unchanged. With correction for unstirred layer effects, it was apparent that the jejunum of diabetic rats was in fact more permeable to decanoic and lauric acid as well as to cholesterol. The results suggest that (i) in diabetic rats the effective resistance of the unstirred water layer between the jejunal lumen and the brush border membrane is lower; (ii) the differences in unstirred layer resistance between the diabetic and control animals obscure the changes in the kinetic constants (Pd, Km, [Formula: see text]) describing the uptake of galactose, medium chain length fatty acids and cholesterol; and (iii) the kinetic changes in nutrient uptake observed in vitro may be confirmed in vivo once the effect of intestinal unstirred layers has been taken into account.

1973 ◽  
Vol 134 (4) ◽  
pp. 1067-1081 ◽  
Author(s):  
Anthony McAllister ◽  
S. P. Allison ◽  
Philip J. Randle

1. The extractions of glucose, lactate, pyruvate and free fatty acids by dog heart in vivo were calculated from measurements of their arterial and coronary sinus blood concentration. Elevation of plasma free fatty acid concentrations by infusion of intralipid and heparin resulted in increased extraction of free fatty acids and diminished extractions of glucose, lactate and pyruvate by the heart. It is suggested that metabolism of free fatty acids by the heart in vivo, as in vitro, may impair utilization of these substrates. These effects of elevated plasma free fatty acid concentrations on extractions by the heart in vivo were reversed by injection of dichloroacetate, which also improved extraction of lactate and pyruvate by the heart in vivo in alloxan diabetes. 2. Sodium dichloroacetate increased glucose oxidation and pyruvate oxidation in hearts from fed normal or alloxan-diabetic rats perfused with glucose and insulin. Dichloroacetate inhibited oxidation of acetate and 3-hydroxybutyrate and partially reversed inhibitory effects of these substrates on the oxidation of glucose. In rat diaphragm muscle dichloroacetate inhibited oxidation of acetate, 3-hydroxybutyrate and palmitate and increased glucose oxidation and pyruvate oxidation in diaphragms from alloxan-diabetic rats. Dichloroacetate increased the rate of glycolysis in hearts perfused with glucose, insulin and acetate and evidence is given that this results from a lowering of the citrate concentration within the cell, with a consequent activation of phosphofructokinase. 3. In hearts from normal rats perfused with glucose and insulin, dichloroacetate increased cell concentrations of acetyl-CoA, acetylcarnitine and glutamate and lowered those of aspartate and malate. In perfusions with glucose, insulin and acetate, dichloroacetate lowered the cell citrate concentration without lowering the acetyl-CoA or acetylcarnitine concentrations. Measurements of specific radioactivities of acetyl-CoA, acetylcarnitine and citrate in perfusions with [1-14C]acetate indicated that dichloroacetate lowered the specific radio-activity of these substrates in the perfused heart. Evidence is given that dichloroacetate may not be metabolized by the heart to dichloroacetyl-CoA or dichloroacetylcarnitine or citrate or CO2. 4. We suggest that dichloroacetate may activate pyruvate dehydrogenase, thus increasing the oxidation of pyruvate to acetyl-CoA and acetylcarnitine and the conversion of acetyl-CoA into glutamate, with consumption of aspartate and malate. Possible mechanisms for the changes in cell citrate concentration and for inhibitory effects of dichloroacetate on the oxidation of acetate, 3-hydroxybutyrate and palmitate are discussed.


1987 ◽  
Vol 10 (4) ◽  
pp. 180-187 ◽  
Author(s):  
YUJI KUROSAKI ◽  
SHINICHI HISAICHI ◽  
CHIEKO HAMADA ◽  
TAIJI NAKAYAMA ◽  
TOSHIKIRO KIMURA

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Foo Sok Yen ◽  
Chan Shu Qin ◽  
Sharryl Tan Shi Xuan ◽  
Puah Jia Ying ◽  
Hong Yi Le ◽  
...  

Diabetes mellitus is a metabolic disorder with chronic high blood glucose levels, and it is associated with defects in insulin secretion, insulin resistance, or both. It is also a major public issue, affecting the world's population. This disease contributes to long-term health complications such as dysfunction and failure of multiple organs, including nerves, heart, blood vessels, kidneys, and eyes. Flavonoids are phenolic compounds found in nature and usually present as secondary metabolites in plants, vegetables, and fungi. Flavonoids possess many health benefits such as anti-inflammatory and antioxidant activities, and naturally occurring flavonoids contribute to antidiabetic effects.Many studies conducted in vivo and in vitro have proven the hypoglycemic effect of plant flavonoids. A large number of studies showed that flavonoids hold positive results in controlling the blood glucose level in streptozotocin (STZ)-induced diabetic rats and further prevent the complications of diabetes. The future development of flavonoid-based drugs is believed to provide significant effects on diabetes mellitus and diabetes complication diseases. This review aims at summarizing the various types of flavonoids that function as hyperglycemia regulators such as inhibitors of α-glucosidase and glucose cotransporters in the body. This review article discusses the hypoglycemic effects of selected plant flavonoids namely quercetin, kaempferol, rutin, naringenin, fisetin, and morin. Four search engines, PubMed, Google Scholar, Scopus, and SciFinder, are used to collect the data.


1991 ◽  
Vol 66 (3) ◽  
pp. 467-477
Author(s):  
M. V. Pahl ◽  
A. Barbari ◽  
N. D. Vaziri ◽  
D. Hollander ◽  
M. Yazdani ◽  
...  

Linoleic acid (LA) transport in rats with experimental short-term and long-term renal failure (RF) was compared with that of sham-operated normal animals on liberal food intake and pair-fed animals. The perfusions in vivo and incubations in vitro were conducted using a micellar solution containing a wide range of LA concentrations. Both absorption in vivo and uptake in vitro of LA were significantly reduced in animals with short-term RF. Lipid extraction and separation by thin-layer chromatography revealed a marked LA trapping as trilinolein (TL) in the perfused intestinal tissue in the short-term RF group. The esterification process, as defined by the rate of LA incorporation into TL, was moderately reduced in short-term RF animals. The thickness of the unstirred water layer showed no significant difference among the groups studied. In contrast, animals with long-term RF exhibited normal absorption of LA in vivo at all concentrations tested. In conclusion, LA absorption is reduced in short-term RF and restored in long-term RF. Several steps including LA transport into and TL transport out of the enterocyte and the esterification process were impaired in short-term RF. These changes are not due to alteration in the unstirred water layer, anorexia, weight loss or a rapid effect of uraemic chemical environment or circulatory factors.


1981 ◽  
Vol 241 (3) ◽  
pp. G270-G274
Author(s):  
A. B. Thomson ◽  
B. D. O'Brien

The rate of uptake (Jd) of cholesterol into the intestine is influenced by the effective resistance of the unstirred water layer, the concentration of the probe molecule at the aqueous-membrane interface, and the passive permeability characteristics of the membrane. This study was undertaken to determine the influence of the bile acid micelle and the unstirred water layer on the Jd of cholesterol into rabbit jejunum, using everted sacs, full-thickness biopsies, and disks. When the bulk phase was stirred and the resistance of the unstirred layer was low, there was a linear relation between cholesterol concentration in the bulk phase and Jd when the concentration of taurodeoxycholic acid (TDC) was constant, but increasing TDC in the presence of a constant concentration of cholesterol was associated with a decline in Jd. When the concentration of both TDC and cholesterol was varied but the ratio of TDC to cholesterol was maintained constant, Jd increased slightly. The Jd of cholesterol was higher into sacs than into biopsies, which in turn was greater than into disks; Jd into disks was much lower when the resistance of the unstirred layer was high. These results suggest that 1) the bile acid micelle serves to provide a reservoir for partitioning of the cholesterol from the micelle into the aqueous phase from which the cholesterol is absorbed; 2) the Jd of cholesterol into disks of jejunum is influenced by the effective resistance of the unstirred water layer; and 3) although the quantity of cholesterol Jd varies markedly between sacs, biopsies, and disks, the qualitative aspects of the role of the bile acid micelle in cholesterol absorption were similar using the different in vitro techniques.


Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6926
Author(s):  
Peiwen Zhang ◽  
Xinrong Li ◽  
Shunhua Zhang ◽  
Shuang Wu ◽  
Qian Xiao ◽  
...  

Excessive fat accumulation can lead to obesity, diabetes, hyperlipidemia, atherosclerosis, and other diseases. MicroRNAs are a class of microRNAs that regulate gene expression and are highly conserved in function among species. microRNAs have been shown to act as regulatory factors to inhibit fat accumulation in the body. We found that miR-370-3p was expressed at lower levels in the fat mass of mice on a high-fat diet than in mice on a normal control diet. Furthermore, our data showed that the overexpression of miR-370-3p significantly suppressed the mRNA expression levels of adipogenic markers. Thus, miR-370-3p overexpression reduced lipid accumulation. Conversely, the inhibition of miR-370-3p suppressed 3T3-L1 preadipocyte proliferation and promoted preadipocyte differentiation. In addition, Mknk1, a target gene of miR-370-3p, plays an opposing role in preadipocyte proliferation and differentiation. Moreover, consistent results from in vitro as well as in vivo experiments suggest that the inhibition of fat accumulation by miR-370-3p may result from the inhibition of saturated fatty acids that promote the accumulation of polyunsaturated fatty acids. In conclusion, these results suggest that miR-370-3p plays an important role in adipogenesis and fatty acid metabolism through the regulation of Mknk1.


2017 ◽  
Vol 95 (11) ◽  
pp. 1319-1326 ◽  
Author(s):  
Zsófia Mezei ◽  
Sándor Váczi ◽  
Viktória Török ◽  
Csaba Stumpf ◽  
Rita Ónody ◽  
...  

Hyperglycemia, hyperlipidemia, and free radicals result in platelet activation and atherogenesis. Kisspeptin (KP) is able to regulate metabolism, hemostasis, and the development of atherosclerosis. We examined whether platelet aggregation of streptozotocin-induced diabetic rats depends on the inducer type and if KP-13 and RF-9 (a kisspeptin receptor modifier) can influence platelet function. We measured the speed and the maximum of aggregation, along with the area under the curve. Serum glucose and calcium levels and urine formation of diabetic animals increased, while the body mass and platelet count decreased. Collagen was the most effective inducer of platelet aggregation. The aggregability of nondiabetic platelets was elevated in the presence of 5 × 10−8 mol/L KP-13. This effect was less expressed in diabetic animals. The effectivity of RF-9 was stronger than that of KP-13 in nondiabetic platelets, however it was ineffective in diabetic animals. RF-9 pre-treatment did not change the effects of 5 × 10−8 mol/L KP-13 in either animal group. The in vivo activation of diabetic platelets, which may be due to elevated serum calcium, induces thrombocytopenia and may lead to reduced in vitro aggregability. We could not demonstrate the antagonistic effect of RF-9 against KP-13 in isolated platelets.


2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.


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