title: Spontaneous obesity-linked type 2 diabetes in the absence of islet amyloid in a cynomolgus monkey infected with bovine spongiform encephalopathy.
abstract: A 9-year-old cynomolgus monkey (Macaca fascicularis) infected orally with bovine spongiform encephalopathy (BSE) was presented for necropsy following euthanasia 4 years post infection (p.i.). This macaque R984 was exposed to a BSE dose that causes a simian form of variant Creutzfeldt-Jakob disease (vCJD) within 5 years p.i. in other macaques. All orally BSE-infected macaques developed a significant weight gain within the first 2 years p.i. compared with non-BSE-infected age- and sex-matched control animals, suggesting increased risk of type 2 diabetes (T2D). In contrast, macaque R984 developed rapid weight loss, hyperglycemia, and glucosuria and had to be euthanatized 4 years p.i. before clinical signs of vCJD. Pancreas histopathological evaluation revealed severe islet degeneration but, remarkably, no islet amyloid deposits were present. Immunostaining of pancreas sections for insulin and glucagon confirmed the loss of endocrine cells. In addition, prions were present in the adenohypophysis but not in other areas of the brain, indicating centripetal prion spread from the gut during the preclinical phase of BSE infection. Plasma glucose and insulin concentrations of macaque R984 became abnormal with age and resembled T2D. This unusual case of spontaneous T2D in the absence of islet amyloid deposits could have been due to early prion spread from the periphery to the endocrine system or could have occurred spontaneously.
authors: Institute for Clinical Diabetology, German Diabetes Center, Auf'm Hennekamp 65, D-40225 Düsseldorf, Germany. Email: alexander.strom@ddz.uni-duesseldorf.de.
authors: A
authors: A
authors: Strom
authors: B
authors: B
authors: Yutzy
authors: C
authors: C
authors: Kruip
authors: I
authors: I
authors: Völker
authors: N C
authors: NC
authors: Schloot
authors: M
authors: M
authors: Roden
authors: F W
authors: FW
authors: Scott
authors: J
authors: J
authors: Löwer
authors: E
authors: E
authors: Holznagel
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002417:Cattle; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000473:pathology*; D016643:Encephalopathy, Bovine Spongiform / Q000150:complications*; D005260:Female; D006652:Histological Techniques / Q000662:veterinary; D007328:Insulin / Q000097:blood; D058228:Islet Amyloid Polypeptide / Q000378:metabolism; D008252:Macaca fascicularis; D008992:Monkey Diseases / Q000473:pathology*; D009765:Obesity / Q000150:complications*; D010179:Pancreas / Q000473:pathology; D012737:Sex Factors
chemical_list: D001786:Blood Glucose; D007328:Insulin; D058228:Islet Amyloid Polypeptide
keywords: Macaca fascicularis; bovine spongiform encephalopathy; diabetes