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CRO diabetes
Metabolic Diseases

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Diabetes

Diabetes is an increasing health and economic burden in the world. About 422 million people worldwide suffer from diabetes and 1.6 million death are directly related to diabetes each year. In patients with diabetes type 1 the pancreas produces little or no insulin by itself. Diabetes type 2 is characterized by an insulin resistance and it is more common with an increasing prevalence in all countries.

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Diabetes - In vivo Models​

  • Genetic models: db/db mice, ob/ob mice, NOD mice 

Db/db and ob/ob mice have a defect in the leptin system.​ Obesity, insulin resistance, development of diabetes and diabetic complications characterize these models. Follow up in these models is 12 - 20 weeks.

  • Chemically-induced diabetes models: Streptozotozin, Alloxan

Streptozotozin selectively damages the insulin producing beta cells in the pancreas. Follow up in this model is

6 - 14 weeks.​

  • Diet induced obesity

We use a custom-made high fat diet to induce obesity and insulin resistance.

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Available Readouts

  1. Development of diabetes

    • Blood glucose measurements, HbA1C

    • Body weight

  2. Feed / Water intake​

  3. Measurement of insulin resistance

    • Homer Index

    • Oral glucose tolerance test (OGTT)

    • Intraperitoneal glucose tolerance test (IPGTT)

    • Hyperinsulinemic euglycemic clamp in swiveled animals (on request)

  4. Diabetic nephropathy - Diabetic nephropathy is characterized by early vascular dysfunction and increasing matrix accumulation in the kidney leading to proteinuria, glomerulosclerosis and interstitial fibrosis

    • Creatinine and BUN clearance

    • Glomerular filtration rate (GFR)

    • Albuminuria

    • Morphology (mesangial sclerosis and nodular sclerosis, arteriolar hyalinosis, glomerular basement thickening, tubule-interstitial fibrosis)

    • Immunohistochemistry and RT-PCR for specific markers of interest

    • Inflammation (cytokine/chemokine profile in serum and kidney tissue, immunophenotyping of infiltrating leukocytes)

  5. Diabetic neuropathy

    • Sensory and motor nerve conductance velocity

    • Histological and immunhistological analysis (upon request)

  6. Diabetic retinopathy

    • Histological and immunhistological analysis

    • Western blotting and RT-PCR

  7. Diabetic cardiomyopathy

    • Myocardial hypertrophy

    • Cardiac histology (extracellular matrix deposition, thickening of endothelial  basal membrane, fibrosis)

    • Cardiac immunohistochemistry (collagen, TGFb, p-AKT)

    • Expression of atrial (ANP) and brain (BNP) diuretic peptides

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Diabetes
diabetes model
in vivo

Techniques

  1. Clinical chemistry

  2. Metabolic cages

  3. Blood pressure analysis

  4. Assessment of Glomerular Filtration Rate (GFR)

  5. Nerve conduction velocity

  6. Flow cytometry including Bead-based flow cytometry

  7. Histology (H&E, Masson Trichrome, Periodic Acid Schiff (PAS) staining)

  8. Immunohistochemistry

  9. ELISA

  10. Molecular biology (Real-Time PCR, Western blot)

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Need further Readouts? We routinely develop new models to fit our cutomer needs.

 

Speak with us for tailor-made solutions!

Contact Phenos today!

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in vitro

Diabetes - In vitro models

In vitro we investigate cellular mechanisms which can lead to the discovery of new molecular drug targets. Furtheremore new agents can be evaluated which have the potential to be used in treatment.

We either use primary cell cultures or transformed cell lines.

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Need further Readouts or cell lines? We routinely develop new models to fit our cutomer needs.

 

Speak with us for tailor-made solutions!

 

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Publications
Obesity

Diabetes - relevant Publications

 

Dual inhibition of classical protein kinase C-α and protein kinase C-β isoforms protects against experimental murine diabetic nephropathy.

Menne J, Shushakova N, Bartels J, Kiyan Y, Laudeley R, Haller H, Park JK, Meier M. Diabetes. 2013 Apr;62(4):1167-74. PMID: 23434935

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Podocytic PKC-alpha is regulated in murine and human diabetes and mediates nephrin endocytosis.

Tossidou I, Teng B, Menne J, Shushakova N, Park JK, Becker JU, Modde F, Leitges M, Haller H, Schiffer M. PLoS One. 2010 Apr 16;5(4):e10185. PMID: 20419132

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Deletion of Protein Kinase C-{varepsilon} Signaling Pathway Induces Glomerulosclerosis and Tubulointerstitial Fibrosis In Vivo.

Meier M, Menne J, Park JK, Holtz M, Gueler F, Kirsch T, Schiffer M, Mengel M, Lindschau C, Leitges M, Haller H. J Am Soc Nephrol. 2007 Apr; 18(4): 1190-8. Epub 2007 Mar 14. PMID: 17360953

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Deletion of protein kinase C-beta isoform in vivo reduces renal hypertrophy but not albuminuria in the streptozotocin-induced diabetic mouse model.

Meier M, Park JK, Overheu D, Kirsch T, Lindschau C, Gueler F, Leitges M, Menne J, Haller H. Diabetes. 2007 Feb; 56(2): 346-54. PMID: 17259378

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Nephrin loss in experimental diabetic nephropathy is prevented by deletion of protein kinase C alpha signaling in-vivo.

Menne J, Meier M, Park JK, Boehne M, Kirsch T, Lindschau C, Ociepka R, Leitges M, Rinta-Valkama J, Holthofer H, Haller H. Kidney Int. 2006 Oct; 70(8): 1456-62. Epub 2006 Sep 6. PMID: 16955103

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Obesity

Obesity and hyperlipidemia are common medical problems and major risk factors for cardiovascular disease, diabetes, cancer and other disorders.

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In vivo Models

We use the following models to study weight lowering effects and anti-lipidemic effects of drugs.

We also use these models to analyse mechanisms of atherosclerosis.

 

1.  Hyperlipidemia (genetic models)

We use the apoE deficient mouse. Under a high fat diet this mice develop severe arterial lesions.

 

2.  Diet induced hyperlipidemia

In wild type mice a high fat diet leads to hyperlipidemia, but arteriosclerotic lesions are not very prominent.

 

3.  Obesity (genetic models)

The apoE mice and the db/db and ob/ob mice develop obesity.

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4.  Diet induced obesity

We use a high fat diet to induce obesity.

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Phenos - your independent contract research organisation

Contact us today. We routinely develop new models to fit your needs.

CRO obesity
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