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Updated: Jun 12, 2026
Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Carnosinase-1 Knock-Out Reduces Kidney Fibrosis in Type-1 Diabetic Mice on High Fat Diet
Tilman Pfeffer1,2, Charlotte Wetzel1, Philip Kirschner1
1Centre for Paediatric and Adolescent Medicine, University of Heidelberg, 69120 Heidelberg, Germany.
Abstract:
Carnosine and anserine supplementation markedLy reduce diabetic nephropathy in rodents. The mode of nephroprotective action of both dipeptides in diabetes, via local protection or improved systemic glucose homeostasis, is uncertain. Global carnosinase-1 knockout mice (Cndp1-KO) and wild-type littermates (WT) on a normal diet (ND) and high fat diet (HFD) (n = 10/group), with streptozocin (STZ)-induced type-1 diabetes (n = 21-23/group), were studied for 32 weeks. Independent of diet, Cndp1-KO mice had 2- to 10-fold higher kidney anserine and carnosine concentrations than WT mice, but otherwise a similar kidney metabolome; heart, liver, muscle and serum anserine and carnosine concentrations were not different. Diabetic Cndp1-KO mice did not differ from diabetic WT mice in energy intake, body weight gain, blood glucose, HbA1c, insulin and glucose tolerance with both diets, whereas the diabetes-related increase in kidney advanced glycation end-product and 4-hydroxynonenal concentrations was prevented in the KO mice. Tubular protein accumulation was lower in diabetic ND and HFD Cndp1-KO mice, interstitial inflammation and fibrosis were lower in diabetic HFD Cndp1-KO mice compared to diabetic WT mice. Fatalities occurred later in diabetic ND Cndp1-KO mice versus WT littermates. Independent of systemic glucose homeostasis, increased kidney anserine and carnosine concentrations reduce local glycation and oxidative stress in type-1 diabetic mice, and mitigate interstitial nephropathy in type-1 diabetic mice on HFD.
Insights
Increased kidney carnosine and anserine levels protect against diabetic nephropathy by reducing local oxidative stress and glycation. This finding offers new insights into managing kidney disease in type-1 diabetes.
Area of Science:
- Biochemistry
- Nephrology
- Metabolic Diseases
Background:
- Carnosine and anserine are dipeptides known to reduce diabetic nephropathy in rodents.
- The precise mechanism of their nephroprotective action, whether local or systemic, remains unclear.
Purpose of the Study:
- To investigate the role of kidney carnosine and anserine concentrations in diabetic nephropathy.
- To determine if elevated levels of these dipeptides independently affect kidney protection, irrespective of systemic glucose control.
Main Methods:
- Global carnosinase-1 knockout (Cndp1-KO) and wild-type (WT) mice were studied under normal and high-fat diet conditions.
- Streptozotocin (STZ)-induced type-1 diabetes was established in mice, and they were observed for 32 weeks.
- Kidney metabolomes, glucose homeostasis markers, and indicators of nephropathy were analyzed.
Main Results:
- Cndp1-KO mice exhibited significantly higher kidney anserine and carnosine levels than WT mice, without differences in systemic glucose control.
- The diabetes-related increase in kidney advanced glycation end-products and oxidative stress markers was prevented in Cndp1-KO mice.
- Diabetic Cndp1-KO mice showed reduced tubular protein accumulation and, on HFD, less interstitial inflammation and fibrosis compared to WT mice.
Conclusions:
- Elevated kidney carnosine and anserine concentrations independently reduce local glycation and oxidative stress in type-1 diabetic mice.
- These dipeptides mitigate interstitial nephropathy, particularly in diabetic mice on a high-fat diet.
- The findings suggest a localized protective effect of carnosine and anserine within the kidney.
