scholarly journals Effect of Insulin on Proximal Tubules Handling of Glucose: A Systematic Review

2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Ricardo Pereira-Moreira ◽  
Elza Muscelli
Keyword(s):  
Glucose Transport ◽  
Insulin Action ◽  
Current Knowledge ◽  
Sglt2 Inhibitor ◽  
Proximal Tubules ◽  
Human Studies ◽  
Glucose Disposal ◽  
Diabetic Patients ◽  
Insulin Effect ◽  
Renal Gluconeogenesis

Renal proximal tubules reabsorb glucose from the glomerular filtrate and release it back into the circulation. Modulation of glomerular filtration and renal glucose disposal are some of the insulin actions, but little is known about a possible insulin effect on tubular glucose reabsorption. This review is aimed at synthesizing the current knowledge about insulin action on glucose handling by proximal tubules. Method. A systematic article selection from Medline (PubMed) and Embase between 2008 and 2019. 180 selected articles were clustered into topics (renal insulin handling, proximal tubule glucose transport, renal gluconeogenesis, and renal insulin resistance). Summary of Results. Insulin upregulates its renal uptake and degradation, and there is probably a renal site-specific insulin action and resistance; studies in diabetic animal models suggest that insulin increases renal SGLT2 protein content; in vivo human studies on glucose transport are few, and results of glucose transporter protein and mRNA contents are conflicting in human kidney biopsies; maximum renal glucose reabsorptive capacity is higher in diabetic patients than in healthy subjects; glucose stimulates SGLT1, SGLT2, and GLUT2 in renal cell cultures while insulin raises SGLT2 protein availability and activity and seems to directly inhibit the SGLT1 activity despite it activating this transporter indirectly. Besides, insulin regulates SGLT2 inhibitor bioavailability, inhibits renal gluconeogenesis, and interferes with Na+K+ATPase activity impacting on glucose transport. Conclusion. Available data points to an important insulin participation in renal glucose handling, including tubular glucose transport, but human studies with reproducible and comparable method are still needed.

Dual mechanism of insulin action on human skeletal muscle: identification of an indirect component not mediated by FFA

1991 ◽  
Vol 260 (3) ◽  
pp. E389-E394 ◽  
Author(s):  
B. Capaldo ◽  
R. Napoli ◽  
P. Di Bonito ◽  
G. Albano ◽  
L. Sacca
Keyword(s):  
Skeletal Muscle ◽  
Insulin Action ◽  
Human Skeletal Muscle ◽  
Insulin Infusion ◽  
Glucose Disposal ◽  
Heparin Infusion ◽  
Insulin Effect ◽  
Infusion Group ◽  
Group I ◽  
Group Ii

To determine whether insulin action on human skeletal muscle is entirely accounted for by a direct effect of insulin per se, we quantitated forearm glucose uptake (FGU) in two groups of normal subjects under conditions of identical forearm tissue insulinization (approximately 90 microU/ml) induced by means of systemic (group I) or intrabrachial insulin infusion (group II). With this approach, a difference of FGU between the two groups is demonstrative of the operation of indirect mechanisms in insulin action. During insulin infusion in group I, euglycemia was maintained by a variable glucose infusion, whereas arterial free fatty acid (FFA) concentration fell below 0.1 mM. In group II, arterial concentrations of both glucose and FFA remained unchanged, indicating that insulin effect was indeed restricted to the forearm tissues. With local insulin administration, FGU reached levels approximately 40% lower than those achieved with systemic insulin infusion (P less than 0.01-0.005). To determine whether this difference could be attributed to the fall in FFA concentration associated with systemic insulinization, FGU was also quantitated during a systemic insulin plus heparin infusion (group III) to maintain FFA at their basal levels. In this condition, insulin-stimulated FGU was not different from that observed in group I. These data demonstrate that 1) insulin action on skeletal muscle glucose disposal is mediated by a direct as well as an indirect component, and 2) the maintenance of basal FFA does not affect insulin-stimulated FGU, indicating that the indirect component of insulin action is mediated by a different mechanism.

Plasma vitamin C affects glucose homeostasis in healthy subjects and in non-insulin-dependent diabetics

1994 ◽  
Vol 266 (2) ◽  
pp. E261-E268 ◽  
Author(s):  
G. Paolisso ◽  
A. D'Amore ◽  
V. Balbi ◽  
C. Volpe ◽  
D. Galzerano ◽  
...  
Keyword(s):  
Vitamin C ◽  
Healthy Subjects ◽  
Insulin Action ◽  
Relative Increase ◽  
Whole Body ◽  
Glucose Disposal ◽  
Diabetic Patients ◽  
Plasma Vitamin ◽  
Arterial Blood ◽  
Insulin Dependent

In aged healthy (n = 10) and non-insulin-dependent (type II) diabetic (n = 10) subjects matched for age [67.3 +/- 0.5 vs. 68.0 +/- 0.4 yr, P = not significant (NS)], body mass index (25.7 +/- 0.7 vs. 26.0 +/- 0.2 kg/m2, P = NS), gender ratio [6 males (M)/4 females (F) vs. 5 M/5 F], and mean arterial blood pressure (104 +/- 6 vs. 105 +/- 9 mmHg, P = NS), we determined the changes in insulin secretion and action after vitamin C infusion and the relative increase in plasma vitamin C levels. At the highest vitamin C infusion rate (0.9 mmol/min) the increase in plasma vitamin C levels did not affect B cell response to glucose, but it improved Conard's K values and whole body glucose disposal in healthy subjects and in diabetic patients. In both groups of subjects vitamin C-mediated increase in insulin action was mainly due to an improvement in nonoxidative glucose metabolism. After fasting, plasma vitamin C levels correlated with basal whole body glucose disposal (r = -0.44, P < 0.05; n = 20). After vitamin C infusion, percent change in plasma vitamin C level correlated with the percent decline in membrane microviscosity (r = 0.53, P < 0.01; n = 20) and increase in whole body glucose disposal (r = 0.63, P < 0.003; n = 20). In conclusion, plasma vitamin C levels seem to play a role in the modulation of insulin action in aged healthy and diabetic subjects.

Short-term hyperglycemia and hyperinsulinemia improve insulin action but do not alter glucose action in normal humans

1992 ◽  
Vol 262 (4) ◽  
pp. E518-E523 ◽  
Author(s):  
S. E. Kahn ◽  
R. N. Bergman ◽  
M. W. Schwartz ◽  
G. J. Taborsky ◽  
D. Porte
Keyword(s):  
Insulin Sensitivity ◽  
Basal Insulin ◽  
Insulin Action ◽  
Insulin Response ◽  
Glucose Infusion ◽  
Glucose Disposal ◽  
Second Phase ◽  
Insulin Effect ◽  
Glucose Effectiveness ◽  
Mild Hyperglycemia

Tissue glucose uptake occurs by insulin-dependent and insulin-independent mechanisms. To evaluate the effect of mild hyperglycemia and hyperinsulinemia on the parameters responsible for glucose disposal, glucose (1.17 mmol/min) or saline was infused into six healthy male subjects (age 25-38 yr, body mass index 22.1-26.3 kg/m2) for 24 h. Thereafter, while the infusion continued, indexes of insulin sensitivity (SI), glucose effectiveness at basal insulin (SG), basal insulin effect (BIE = SI x basal insulin), and glucose effectiveness at zero insulin (GEZI = SG - BIE) were measured using Bergman's minimal model of insulin action. GEZI provides a measure of the efficiency of glucose to accelerate its own disposal independent of insulin. Twenty-four hours of glucose infusion increased the basal plasma glucose (5.1 +/- 0.1 to 6.4 +/- 0.2 mM, P = 0.001) and insulin (79 +/- 8 to 174 +/- 31 pM, P less than 0.05) levels. Hyperglycemia was also associated with an increase in the insulin response, predominantly in the second-phase component (138 +/- 31 to 258 +/- 66 pM, P less than 0.05). SI (4.8 +/- 1.0 to 8.2 +/- 1.6 x 10(-5) min-1.pM-1, P less than 0.05) and SG (1.7 +/- 0.1 to 2.5 +/- 0.3 x 10(-2) min-1, P less than 0.05) both increased after glucose infusion. The increase in SG was entirely due to the combined increase in basal insulin and insulin sensitivity (BIE 0.4 +/- 0.1 to 1.2 +/- 0.1 x 10(-2) min-1, P = 0.001) since GEZI did not change at all (1.3 +/- 0.1 vs. 1.3 +/- 0.3 x 10(-2) min-1, P = not significant). From these data we conclude that, in normal subjects, the mild hyperglycemia and hyperinsulinemia occurring during a prolonged glucose infusion improves glucose disposal in the basal state by increasing insulin secretion and insulin sensitivity but does not enhance glucose effectiveness independent of insulin. Both of these changes thus tend to minimize the development of hyperglycemia.

Insulin Action on Glucose Transport in Isolated Skeletal Muscle from Patients with Liver Cirrhosis

1994 ◽  
Vol 29 (1) ◽  
pp. 71-76 ◽  
Author(s):  
U. Johansson ◽  
L. S. Eriksson ◽  
D. Galuska ◽  
J. R. Zierath ◽  
H. Wallberg-henriksson
Keyword(s):  
Skeletal Muscle ◽  
Liver Cirrhosis ◽  
Glucose Transport ◽  
Insulin Action

Adenosine effects upon insulin action on lipolysis and glucose transport in human adipocytes

1995 ◽  
Vol 144 (2) ◽  
pp. 147-151 ◽  
Author(s):  
Lesley Heseltine ◽  
Judith M. Webster ◽  
Roy Taylor
Keyword(s):  
Glucose Transport ◽  
Insulin Action ◽  
Human Adipocytes

scholarly journals Development of osmotic vacuolization of proximal tubular epithelial cells following treatment with sodium-glucose transport protein 2 inhibitors in type II diabetes mellitus patients-3 case reports

2021 ◽  
Author(s):  
Shun Watanabe ◽  
Naoki Sawa ◽  
Hiroki Mizuno ◽  
Masayuki Yamanouchi ◽  
Tatsuya Suwabe ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Type Ii Diabetes ◽  
Sglt2 Inhibitor ◽  
Type Ii Diabetes Mellitus ◽  
Proximal Tubules ◽  
Type Ii ◽  
Tubular Epithelial Cells ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular ◽  
Standard Weight

AbstractWe encountered 3 cases of acute kidney injury that occurred after treatment with a SGLT2 inhibitor. In case 1, serum creatinine increased from 1.65 to 3.0 mg/dL, in case 2, serum creatinine increased from 1.03 to 1.21 mg/dL, and in case 3, serum creatinine increased from 0.8 to 1.1 mg/dL. Renal biopsy showed isometric vacuolization on tubules, that was completely negative for Periodic acid-Schiff (PAS) stain in case 1, and was partially negative for PAS stain in case 2 and 3, consistent with osmotic vacuolization. Immunohistochemical analysis showed positive staining for CD138 and CD10 indicating the proximal tubules in the vacuolar lesions. 3 patients were obese with body mass index of more than 30, and showed an increase in serum renin. In conclusion, in type II diabetes mellitus (T2DM), individuals that remain within their standard weight range, SGLT2 inhibitor treatment does not result in osmotic vacuolization of proximal tubular epithelial cells and AKI. However, treatment with a SGLT2 inhibitor may cause damage of the proximal tubules resulting in AKI in T2DM individuals who do not remain within their standard weight range, due to an overdose lavage of sugar in the urine and dehydration.

scholarly journals Low-Dose Acrolein, an Endogenous and Exogenous Toxic Molecule, Inhibits Glucose Transport via an Inhibition of Akt-Regulated GLUT4 Signaling in Skeletal Muscle Cells

2021 ◽  
Vol 22 (13) ◽  
pp. 7228
Author(s):  
Ching-Chia Wang ◽  
Huang-Jen Chen ◽  
Ding-Cheng Chan ◽  
Chen-Yuan Chiu ◽  
Shing-Hwa Liu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Protein Expression ◽  
Glucose Uptake ◽  
Glucose Transport ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic

Urinary acrolein adduct levels have been reported to be increased in both habitual smokers and type-2 diabetic patients. The impairment of glucose transport in skeletal muscles is a major factor responsible for glucose uptake reduction in type-2 diabetic patients. The effect of acrolein on glucose metabolism in skeletal muscle remains unclear. Here, we investigated whether acrolein affects muscular glucose metabolism in vitro and glucose tolerance in vivo. Exposure of mice to acrolein (2.5 and 5 mg/kg/day) for 4 weeks substantially increased fasting blood glucose and impaired glucose tolerance. The glucose transporter-4 (GLUT4) protein expression was significantly decreased in soleus muscles of acrolein-treated mice. The glucose uptake was significantly decreased in differentiated C2C12 myotubes treated with a non-cytotoxic dose of acrolein (1 μM) for 24 and 72 h. Acrolein (0.5–2 μM) also significantly decreased the GLUT4 expression in myotubes. Acrolein suppressed the phosphorylation of glucose metabolic signals IRS1, Akt, mTOR, p70S6K, and GSK3α/β. Over-expression of constitutive activation of Akt reversed the inhibitory effects of acrolein on GLUT4 protein expression and glucose uptake in myotubes. These results suggest that acrolein at doses relevant to human exposure dysregulates glucose metabolism in skeletal muscle cells and impairs glucose tolerance in mice.

Influence of short-term dexfenfluramine therapy on glucose and lipid metabolism in obese non-diabetic patients

1993 ◽  
Vol 128 (3) ◽  
pp. 251-258 ◽  
Author(s):  
Per H Andersen ◽  
Bjørn Richelsen ◽  
Jens Bak ◽  
Ole Schmitz ◽  
Niels S Sørensen ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Serum Insulin ◽  
Whole Body ◽  
Glucose Disposal ◽  
Total Serum ◽  
Total Serum Cholesterol ◽  
Diabetic Patients ◽  
Obese Patients ◽  
Short Term ◽  
Glucose And Lipid Metabolism

In a short-term (eight days) double-blind crossover study involving 10 obese patients, the effects of dexfenfluramine on glucose and lipid metabolism were examined. The protocol comprised whole body in vivo measurements (hyperinsulinemic euglycemic clamp in combination with indirect calorimetry) and in vitro studies of isolated adipocytes (lipolysis and glucose transport). All study participants were weight stable during the study period (103.1±3.2, placebo vs 103.3±3.1 kg, dexfenfluramine, NS). The following parameters were significantly reduced after dexfenfluramine treatment: fasting levels of plasma glucose (6.2±0.2 vs 5.7±0.2 mmol/l, p<0.01), serum insulin (168.0±14.5 vs 138.9±7.9 pmol/l, p<0.05), serum C-peptide (0.68±0.03 vs 0.58±0.02 nmol/l, p<0.05) and total serum cholesterol (6.07±0.41 vs 5.48±0.38 mmol/l, p< 0.01). In the basal state glucose oxidation rate was significantly reduced by 36% (p<0.001), whereas non-oxidative glucose disposal was significantly increased by 41% (p<0.01), following dexfenfluramine treatment. Insulin-stimulated (2 mU·kg−1·min−1) glucose disposal rate tended to be increased (18%, p=0.10) after dexfenfluramine. In conclusion, dexfenfluramine possesses beneficial regulatory effects on glucose and lipid metabolism in non-diabetic obese patients, independently of weight loss.

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