scholarly journals The acute regulation of glucose absorption, transport and metabolism in rat small intestine by insulin in vivo

1984 ◽  
Vol 219 (3) ◽  
pp. 1027-1035 ◽  
Author(s):  
G L Kellett ◽  
A Jamal ◽  
J P Robertson ◽  
N Wollen

The effect of acute changes in insulin concentrations in vivo on the absorption, transport and metabolism of glucose by rat small intestine in vitro was investigated. Within 2 min of the injection of normal anaesthetized rats with anti-insulin serum, lactate production and glucose metabolism were respectively diminished to 28% and 21% of normal and the conversion of glucose into lactate became quantitative. These changes correlated with the inhibition of two mucosal enzymes, namely the insulin-sensitive enzyme pyruvate dehydrogenase, and phosphofructokinase, which was shown by cross-over measurements to be the rate-limiting enzyme of glycolysis in mucosa. The proportion of glucose translocated unchanged from the luminal perfusate to the serosal medium was simultaneously increased from 45% to 80%. All the changes produced by insulin deficiency were completely reversed with 2 min when antiserum was neutralized by injection of insulin in vivo. The absorption and transport of 3-O-methylglucose were unaffected by insulin. It is concluded that glucose metabolism in rat small intestine is subject to short-term regulation by insulin in vivo and that glucose absorption and transport are regulated indirectly in response to changes in metabolism. Moreover, transport and metabolism compensate in such a way as to deliver the maximal ‘effective’ amount of glucose to the blood, whether as glucose itself or as lactate for hepatic gluconeogenesis.

1979 ◽  
Vol 57 (6) ◽  
pp. 529-534 ◽  
Author(s):  
M. L. G. Gardner ◽  
Jane A. Plumb

1. Hydrolase activities against three dipeptides were measured in mucosal cytoplasm in unperfused intestines and in mucosal cytoplasm, luminal effluents and serosal secretions after perfusion in vitro and in vivo for 1 h. Intestines in vitro were prepared both from anaesthetized rats and from freshly killed rats. 2. Only 0·6–1·9% of the initial cytoplasmic activity was recovered in the luminal effluent when intestines in vitro were prepared from anaesthetized rats. Recoveries in luminal effluents were similar (1·3–3·3%) during perfusion in vivo. 3. Losses of dipeptidases into the luminal effluent were four to eight times greater when intestines in vitro were prepared from freshly killed animals. 4. Similar losses of dipeptidases into the secretion on to the serosal surface were observed; they too were much greater when intestines were prepared from freshly killed animals. 5. Small losses of mucosal DNA during perfusion were also observed; however, losses of cytoplasmic peptidases were consistently slightly greater. 6. Enzyme loss therefore probably occurs both by sloughing of whole cells and by a more specific process which is greatly influenced by experimental procedure. Caution is necessary in the interpretation of peptide transport experiments in vitro, although the possibility that intraluminal hydrolysis is of physiological significance must not be excluded.


1979 ◽  
Vol 41 (1) ◽  
pp. 47-51 ◽  
Author(s):  
D. F. Evered ◽  
F. Sadoogh-Abasian

1. The disaccharide lactulose (galactosyl-β-1,4-fructose) was poorly absorbed from rat small intestine in vitro and human mouth in vivo.2. These results confirm indirect clinical evidence of poor absorption from the intestine.3. The presence of calcium ions, or absence of sodium ions, had no effect on lactulose absorption from the buccal cavity.4. The presence of ouabain, or absence of Na+, did not decrease the absorption of lactulose from small intestine.5. It is thought that the mode of transport, in both instances, is by passive diffusion with the concentration gradient.


1975 ◽  
Vol 228 (5) ◽  
pp. 1409-1414
Author(s):  
S Mishkin ◽  
M Yalovsky ◽  
JI Kessler

The uptake and esterification of micellar [3-H]oleate and [14-C] palmitate were uniform along the entire length of the small intestine in vivo. Fatty acids (FA) radioactivity taken up by the small intestine could be described in terms of four functionally distinct compartments analogous to those described in vitro. The KRP-extractable compartment (KEC) and albumin-extractable compartment (AEC) contained reversibly adherent unesterified FA radioactivity, while the tissue free and esterified FA compartments contained irreversibly bound radioactivity. Wheras 27% and 63% of FA uptake were reversibly bound in the KEC and AEC by the most proximal and most distal regions of the small intestine in vitro (15), less than 10% was contained in these compartments in vivo, independent of location. Linear inverse relationships were found betweeen tissue FA esterification and proportion of FA radioactivity present in the KEC,AEC, and the tissue free FA compartment in vivo. These observations allow for the possibility that FA molecules pass through these compartments prior to esterification.


Author(s):  
Baochi Ou ◽  
Hongze Sun ◽  
Jingkun Zhao ◽  
Zhuoqing Xu ◽  
Yuan Liu ◽  
...  

Abstract Background Polo-like kinase 3 (PLK3) has been documented as a tumor suppressor in several types of malignancies. However, the role of PLK3 in colorectal cancer (CRC) progression and glucose metabolism remains to be known. Methods The expression of PLK3 in CRC tissues was determined by immunohistochemistry. Cells proliferation was examined by EdU, CCK-8 and in vivo analyses. Glucose metabolism was assessed by detecting lactate production, glucose uptake, mitochondrial respiration, extracellular acidification rate, oxygen consumption rate and ATP production. Chromatin immunoprecipitation, luciferase reporter assays and co-immunoprecipitation were performed to explore the signaling pathway. Specific targeting by miRNAs was determined by luciferase reporter assays and correlation with target protein expression. Results PLK3 was significantly downregulated in CRC tissues and its low expression was correlated with worse prognosis of patients. In vitro and in vivo experiments revealed that PLK3 contributed to growth inhibition of CRC cells. Furthermore, we demonstrated that PLK3 impeded glucose metabolism via targeting Hexokinase 2 (HK2) expression. Mechanically, PLK3 bound to Heat shock protein 90 (HSP90) and facilitated its degradation, which led to a significant decrease of phosphorylated STAT3. The downregulation of p-STAT3 further suppressed the transcriptional activation of HK2. Moreover, our investigations showed that PLK3 was directly targeted by miR-106b at post-transcriptional level in CRC cells. Conclusion This study suggests that PLK3 inhibits glucose metabolism by targeting HSP90/STAT3/HK2 signaling and PLK3 may serve as a potential therapeutic target in colorectal cancer.


2019 ◽  
Vol 123 (6) ◽  
pp. 619-626
Author(s):  
Yoshihiko Komuro ◽  
Takashi Kondo ◽  
Shingo Hino ◽  
Tatsuya Morita ◽  
Naomichi Nishimura

AbstractTo investigate whether oral intake of highly branched α-glucan isomaltodextrin (IMD) could stimulate ileal glucagon-like peptide-1 (GLP-1) secretion, we examined (1) the digestibility of IMD, (2) the digestion and absorption rates of IMD, in rat small intestine and (3) portal GLP-1 concentration in rats given IMD. In Expt 1, ileorectostomised rats were given a 3 % IMD diet for 10 d. Separately, a 16-h in vitro digestion of IMD, using porcine pancreatic α-amylase and brush-border membrane vesicles from rat small intestine, was conducted. In Expt 2, upon 24-h fasting, rats were given any of glucose, IMD and high-amylose maize starch (HAMS) (1 g/kg of body weight). In Expt 3, caecectomised rats were given 0·2 % neomycin sulphate and a 5 % IMD diet for 10 d. The in vivo and in vitro digestibility of IMD was 70–80 %. The fraction of IMD digested in vitro for the first 120 min was 67 % of that in maize starch. The AUC for 0–120 min of plasma glucose concentration was significantly lower in HAMS group and tended to be lower in IMD group than in the glucose group. Finally, we also observed that, when compared with control rats, glucose of IMD significantly stimulated and improved the concentration of portal active GLP-1 in antibiotic-administered, caecectomised rats. We concluded that IMD was slowly digested and the resulting glucose stimulated GLP-1 secretion in rat small intestine. Oral delivery of slowly released IMD glucose to the small intestine probably exerts important, yet unknown, physiological effects on the recipient.


2016 ◽  
Vol 56 (4) ◽  
pp. 301-309 ◽  
Author(s):  
Ping Li ◽  
Yan Hao ◽  
Feng-Hui Pan ◽  
Min Zhang ◽  
Jian-Qiang Ma ◽  
...  

This study investigates the effectiveness and mechanisms of a serum- and glucocorticoid-inducible kinase 1 (SGK1) inhibitor in counteracting hyperglycemia. In an in vivo experiment, we demonstrated that after an 8-week treatment with an SGK1 inhibitor, the fasting blood glucose and HbA1c level significantly decreased in db/db mice. RT-PCR and western blot analyses revealed that intestinal SGK1 and sodium glucose co-transporter 1 (SGLT1) expression were enhanced in db/db mice. Treatment with an SGK1 inhibitor decreased excessive SGLT1 expression in the intestine of db/db mice. In vitro experiments with intestinal IEC-6 cells showed that the co-administration of an SGK1 inhibitor partly reversed the SGLT1 expression and glucose absorption that were induced by dexamethasone. In conclusion, this study revealed that the favorable effect of an SGK1 inhibitor on hyperglycemia is partly due to decreased glucose absorption through SGLT1 in the small intestine. These data collectively suggest that SGK1 may be a potent target for the treatment of diabetes and other metabolic disorders.


2007 ◽  
Vol 21 (5) ◽  
Author(s):  
Gabriel Baverel ◽  
Bernard Ferrier ◽  
Mireille Martin ◽  
Agnès Conjard ◽  
Fadi Saadé ◽  
...  

1995 ◽  
Vol 23 (2) ◽  
pp. 197-209 ◽  
Author(s):  
Mans Minekus ◽  
Phillipe Marteau ◽  
Robert Havenaar ◽  
Jos H.J. Huis in't Veld

A multicompartmental in vitro model has been described, which simulates the dynamic events occurring within the lumen of the gastrointestinal tract of man and monogastric animals. The accuracy of the model for reproducing in vivo data on gastrointestinal transit, pH, bile salt concentrations and the absorption of glucose was tested. The in vivo conditions simulated in the model were based on studies in healthy human volunteers. Mathematical modelling of gastric and ileal delivery with power exponential equations was used for the computer control of meal transit. The model appeared to reproduce accurately the pre-set data on meal transit, pH and bile salt concentrations in the different gastrointestinal compartments. Glucose absorption from the small intestine was almost complete. This model reproduces very closely the dynamic conditions based on the in vivo situation in monogastric animals and man. Therefore, the model can be an important tool in studying the fate of ingested components (for example, food, microorganisms and medicines) during gastrointestinal transit and, consequently, may contribute to the replacement of studies using laboratory animals.


1981 ◽  
Vol 240 (1) ◽  
pp. G50-G55 ◽  
Author(s):  
A. K. Bhattacharyya

The commonly found plant sterols, beta-sitosterol, campesterol, and stigmasterol, differ structurally from cholesterol only in side chains but are absorbed in much smaller amounts than cholesterol. Because intestinal mucosal cell uptake and esterification are important steps in absorption, these were studied in vivo after feeding the sterols and in vitro using everted sacs of rat small intestine. The studies showed that campesterol uptake was significantly higher than that of beta-sitosterol, whereas stigmasterol uptake was extremely low throughout the intestine. The total intestinal content of campesterol was 2.223 mg/g or about 14% of the dose fed as compared with 1.496 mg/g or 7.4% for beta-sitosterol and only 0.392 mg/g or 2.3% for stigmasterol. Intestinal tissue concentration of esterified campesterol was higher than that of beta-sitosterol, whereas that of esterified stigmasterol was extremely low. The results suggest that campesterol absorption would be higher than that of beta-sitosterol; stigmasterol probably would not be absorbed in any significant amount because of its negligible uptake due to its inability to partition out of the mixed micelles. It appears that the structure of the side chain of a sterol is an important determinant for uptake and esterification, and probably absorption, in the small intestine.


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