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Genetic modulation of diabetic nephropathy among mouse strains with Ins2 Akita mutation.

Wu X, Davis RC, McMillen TS, Schaeffer V, Zhou Z, Qi H, Mazandarani PN, Alialy R, Hudkins KL, Lusis AJ, LeBoeuf RC - Physiol Rep (2014)

Bottom Line: Urine albumin-to-creatinine ratios (ACRs), volume and cystatin C as well as blood urea nitrogen and lipoprotein levels varied significantly among the diabetic strains.ACRs correlated with cystatin C (P = 0.0286), a measure of hyperfiltration and an interstitial tubular marker associated with DN onset in humans suggesting that tubule damage as well as podocyte-stress contributed to reduced kidney function assessed by ACR.However, glomerular hypertrophy and collagen IV content were found to vary significantly among strains suggesting a genetic basis for early onset features of DN.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.

No MeSH data available.


Related in: MedlinePlus

Plasma glucose, insulin, and triglyceride (TG) levels for diabetic and nondiabetic F1 males from a cross between DBA Akita males and a panel of females from various inbred strains. For each graph, the maternal strain is indicated on the horizontal axis and strains are in rank order based on the strain‐average level observed in diabetic mice. (A) Impact of genetic background on plasma glucose levels (mg/dL) is relatively modest among mice of the 28 strains carrying the Akita mutation. There is less than a 2‐fold difference across all strains. (B) As expected, plasma insulin levels (pg/mL) are markedly suppressed in all diabetic F1 males compared to nondiabetic F1 males derived from the same maternal strain. Moreover, insulin levels in diabetic mice were unrelated to levels seen in nondiabetic controls for the same strain. (C) Impact of genetic background on plasma TG levels (mg/dL). *P < 0.05 (n = 3–17 mice/group). To facilitate comparisons among strains, these data are presented in alphabetical strain order in Figure 7‐3A, 3B and 3C at the end of the manuscript.
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fig03: Plasma glucose, insulin, and triglyceride (TG) levels for diabetic and nondiabetic F1 males from a cross between DBA Akita males and a panel of females from various inbred strains. For each graph, the maternal strain is indicated on the horizontal axis and strains are in rank order based on the strain‐average level observed in diabetic mice. (A) Impact of genetic background on plasma glucose levels (mg/dL) is relatively modest among mice of the 28 strains carrying the Akita mutation. There is less than a 2‐fold difference across all strains. (B) As expected, plasma insulin levels (pg/mL) are markedly suppressed in all diabetic F1 males compared to nondiabetic F1 males derived from the same maternal strain. Moreover, insulin levels in diabetic mice were unrelated to levels seen in nondiabetic controls for the same strain. (C) Impact of genetic background on plasma TG levels (mg/dL). *P < 0.05 (n = 3–17 mice/group). To facilitate comparisons among strains, these data are presented in alphabetical strain order in Figure 7‐3A, 3B and 3C at the end of the manuscript.

Mentions: The Akita mutation causes beta‐cell failure as a result of protein aggregate‐induced endoplasmic reticulum stress due to improper folding of proinsulin resulting in reduced insulin production and hyperglycemia (Ron 2002). As expected, Akita mice exhibited severe hyperglycemia at necropsy (~5 months of age) with plasma glucose levels ranging from 465 to 873 mg/dL as compared to values for nondiabetic mice (129 to 264 mg/dL) (Fig. 3A). Of note was that across all of the diabetic strains studied here, there was no significant correlation between plasma glucose levels and ACR (Fig. 2).


Genetic modulation of diabetic nephropathy among mouse strains with Ins2 Akita mutation.

Wu X, Davis RC, McMillen TS, Schaeffer V, Zhou Z, Qi H, Mazandarani PN, Alialy R, Hudkins KL, Lusis AJ, LeBoeuf RC - Physiol Rep (2014)

Plasma glucose, insulin, and triglyceride (TG) levels for diabetic and nondiabetic F1 males from a cross between DBA Akita males and a panel of females from various inbred strains. For each graph, the maternal strain is indicated on the horizontal axis and strains are in rank order based on the strain‐average level observed in diabetic mice. (A) Impact of genetic background on plasma glucose levels (mg/dL) is relatively modest among mice of the 28 strains carrying the Akita mutation. There is less than a 2‐fold difference across all strains. (B) As expected, plasma insulin levels (pg/mL) are markedly suppressed in all diabetic F1 males compared to nondiabetic F1 males derived from the same maternal strain. Moreover, insulin levels in diabetic mice were unrelated to levels seen in nondiabetic controls for the same strain. (C) Impact of genetic background on plasma TG levels (mg/dL). *P < 0.05 (n = 3–17 mice/group). To facilitate comparisons among strains, these data are presented in alphabetical strain order in Figure 7‐3A, 3B and 3C at the end of the manuscript.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4255814&req=5

fig03: Plasma glucose, insulin, and triglyceride (TG) levels for diabetic and nondiabetic F1 males from a cross between DBA Akita males and a panel of females from various inbred strains. For each graph, the maternal strain is indicated on the horizontal axis and strains are in rank order based on the strain‐average level observed in diabetic mice. (A) Impact of genetic background on plasma glucose levels (mg/dL) is relatively modest among mice of the 28 strains carrying the Akita mutation. There is less than a 2‐fold difference across all strains. (B) As expected, plasma insulin levels (pg/mL) are markedly suppressed in all diabetic F1 males compared to nondiabetic F1 males derived from the same maternal strain. Moreover, insulin levels in diabetic mice were unrelated to levels seen in nondiabetic controls for the same strain. (C) Impact of genetic background on plasma TG levels (mg/dL). *P < 0.05 (n = 3–17 mice/group). To facilitate comparisons among strains, these data are presented in alphabetical strain order in Figure 7‐3A, 3B and 3C at the end of the manuscript.
Mentions: The Akita mutation causes beta‐cell failure as a result of protein aggregate‐induced endoplasmic reticulum stress due to improper folding of proinsulin resulting in reduced insulin production and hyperglycemia (Ron 2002). As expected, Akita mice exhibited severe hyperglycemia at necropsy (~5 months of age) with plasma glucose levels ranging from 465 to 873 mg/dL as compared to values for nondiabetic mice (129 to 264 mg/dL) (Fig. 3A). Of note was that across all of the diabetic strains studied here, there was no significant correlation between plasma glucose levels and ACR (Fig. 2).

Bottom Line: Urine albumin-to-creatinine ratios (ACRs), volume and cystatin C as well as blood urea nitrogen and lipoprotein levels varied significantly among the diabetic strains.ACRs correlated with cystatin C (P = 0.0286), a measure of hyperfiltration and an interstitial tubular marker associated with DN onset in humans suggesting that tubule damage as well as podocyte-stress contributed to reduced kidney function assessed by ACR.However, glomerular hypertrophy and collagen IV content were found to vary significantly among strains suggesting a genetic basis for early onset features of DN.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.

No MeSH data available.


Related in: MedlinePlus