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Insulin resistance in adult polycystic kidney disease
K Vareesangthip1, P Tong, R Wilkinson
1Department of Medicine (Nephrology) and Human Diabetes, Medical School, University of Newcastle-upon-Tyne, England, United Kingdom.
Insights
Adult polycystic kidney disease (APKD) patients exhibit insulin resistance and altered leukocyte membrane fluidity. This suggests a potential link between PKD1 gene mutations and metabolic disturbances, possibly increasing cardiovascular risk.
Area of Science:
- Nephrology
- Metabolic Medicine
- Cell Biology
Background:
- Adult polycystic kidney disease (APKD) is a common hereditary disorder affecting kidneys and other organs.
- The PKD1 gene product, a membrane protein, is implicated in cell interactions and tissue distribution.
- Abnormal erythrocyte membrane fluidity in APKD patients suggests potential systemic membrane alterations.
Purpose of the Study:
- To investigate insulin sensitivity in patients with Adult polycystic kidney disease (APKD).
- To explore the relationship between mononuclear leukocyte membrane fluidity and insulin sensitivity in APKD.
- To determine if altered membrane properties contribute to metabolic disturbances in APKD.
Main Methods:
- Insulin sensitivity assessed using a short insulin tolerance test to determine the glucose disappearance rate (Kitt).
- Mononuclear leukocyte membrane fluidity measured via fluorescence anisotropy.
- Comparison of Kitt values and membrane fluidity between 15 APKD patients and 20 age/sex-matched controls.
Main Results:
- APKD patients showed significantly lower Kitt values, indicating insulin resistance compared to normal subjects.
- Leukocyte membrane fluidity was significantly higher (lower anisotropy) in APKD patients.
- Insulin sensitivity (Kitt) was negatively correlated with fasting insulin and positively correlated with leukocyte membrane fluidity.
Conclusions:
- APKD patients exhibit insulin resistance and potential hyperinsulinemia, suggesting an elevated cardiovascular risk.
- Altered leukocyte membrane properties may be the cellular basis for insulin resistance in APKD.
- The findings highlight a potential link between genetic kidney disease and systemic metabolic dysfunction.
Abstract:
Adult polycystic kidney disease (APKD) is a common hereditary disease with renal and extra-renal manifestations. There are at least three genes responsible for this disease. The polycystic kidney disease 1 (PKD1) gene product is a membrane protein involved in cell-cell and cell-matrix interactions and has a widespread tissue distribution. Abnormal membrane fluidity in erythrocytes from APKD patients is due to altered membrane proteins. Membrane fluidity of mononuclear cells is related to whole body insulin sensitivity. Insulin sensitivity might therefore be disturbed in APKD if the erythrocyte membrane abnormality is also present in other cells. Therefore, we investigated insulin sensitivity in 15 APKD patients and 20 normal subjects matched for age and sex. Insulin sensitivity was assessed by a short insulin tolerance test to derive the first-order rate constant for the disappearance of glucose (Kitt) and mononuclear leukocyte membrane fluidity was measured by fluorescence anisotropy. The Kitt value (% mmol.liter-1.min-1) was lower in APKD patients than in normal subjects [median (range) 2.2 (1.5 to 6.3) vs. 4.1 (2.0 to 5.4). P < 0.001]. Fasting plasma insulin concentrations were negatively correlated with the Kitt values (r = -0.66, P < 0.001). Core region anisotropy was significantly lower (higher fluidity) in leukocytes from APKD patients [mean (SEM) 0.164 (0.003) vs. 0.174 (0.001), P < 0.001]. Insulin sensitivity was positively correlated with the fluorescence anisotropy of the core region of leukocyte membranes (r = 0.81, P = 0.0001). In conclusion, APKD patients were insulin resistant and some patients were hyperinsulinemic, which may indicate increased cardiovascular risk. The cellular basis of the insulin resistance may be directly related to the proteins causing the disease or to the general change in membrane properties.