Human Islet Amyloid Polypeptide Expression in COS-1 Cells. A Model of Intracellular Amyloidogenesis

Overview

Journal Am J Pathol

Publisher Elsevier

Specialty Pathology

Date 1995 Sep 1

PMID 7677175

Citations 21

Authors

T D OBrien

P C Butler

D K Kreutter

L A Kane

N L Eberhardt

Affiliations

Soon will be listed here.

Abstract

Non-insulin-dependent diabetes mellitus is characterized by concurrent loss of beta-cells and deposition of islet amyloid derived from islet amyloid polypeptide (IAPP). We have previously demonstrated that IAPP-derived amyloid forms intracellularly in humans with chronic excess insulin expression (eg, insulinoma and insulin receptor antibody-induced insulin resistance). To determine whether overexpression of IAPP results in intracellular amyloid in mammalian cells, we transfected COS cells with vectors expressing amyloidogenic human IAPP or non-amyloidogenic rat IAPP. Transfected COS-1 cells secreted comparable amounts of human IAPP and rat IAPP (2.1 to 2.8 nmol/L/48 hours). After 96 hours, 90% of cells expressing human IAPP contained amyloid fibrils and were degenerating or dead, whereas cells transfected with rat IAPP lacked amyloid and were viable. Thus, overexpression of human IAPP can result in intracellular amyloid formation that is associated with cell death, suggesting that intracellular amyloid may play a role in beta-cell loss in non-insulin-dependent diabetes mellitus.

Citing Articles

Atomic structures of fibrillar segments of hIAPP suggest tightly mated β-sheets are important for cytotoxicity.

Krotee P, Rodriguez J, Sawaya M, Cascio D, Reyes F, Shi D Elife. 2017; 6.

PMID: 28045370 PMC: 5207774. DOI: 10.7554/eLife.19273.

Type 2 diabetes as a protein misfolding disease.

Mukherjee A, Morales-Scheihing D, Butler P, Soto C Trends Mol Med. 2015; 21(7):439-49.

PMID: 25998900 PMC: 4492843. DOI: 10.1016/j.molmed.2015.04.005.

Human IAPP-induced pancreatic β cell toxicity and its regulation by autophagy.

Shigihara N, Fukunaka A, Hara A, Komiya K, Honda A, Uchida T J Clin Invest. 2014; 124(8):3634-44.

PMID: 25036706 PMC: 4109539. DOI: 10.1172/JCI69866.

Expression of wild-type and mutant S20G hIAPP in physiologic knock-in mouse models fails to induce islet amyloid formation, but induces mild glucose intolerance.

Hiddinga H, Sakagashira S, Ishigame M, Madde P, Sanke T, Nanjo K J Diabetes Investig. 2014; 3(2):138-47.

PMID: 24843557 PMC: 4020731. DOI: 10.1111/j.2040-1124.2011.00166.x.

Autophagy protects against human islet amyloid polypeptide-associated apoptosis.

Morita S, Sakagashira S, Shimajiri Y, Eberhardt N, Kondo T, Kondo T J Diabetes Investig. 2014; 2(1):48-55.

PMID: 24843461 PMC: 4008015. DOI: 10.1111/j.2040-1124.2010.00065.x.

References

OBrien T, Rizza R, Carney J, Butler P . Islet amyloidosis in a patient with chronic massive insulin resistance due to antiinsulin receptor antibodies. J Clin Endocrinol Metab. 1994; 79(1):290-2. DOI: 10.1210/jcem.79.1.8027243. View

Rother K, Carney J, Couce M, Charlesworth J, Butler P . Islet amyloid polypeptide in pancreatic tissue of children with persistent hyperinsulinemic hypoglycemia caused by primary islet hyperplasia and nesidioblastosis. J Clin Endocrinol Metab. 1995; 80(6):1956-9. DOI: 10.1210/jcem.80.6.7539820. View

Durie B, Persky B, Soehnlen B, Grogan T, Salmon S . Amyloid production in human myeloma stem-cell culture, with morphologic evidence of amyloid secretion by associated macrophages. N Engl J Med. 1982; 307(27):1689-92. DOI: 10.1056/NEJM198212303072706. View

Glenner G, Wong C . Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem Biophys Res Commun. 1984; 122(3):1131-5. DOI: 10.1016/0006-291x(84)91209-9. View

Wong G, Witek J, Temple P, Wilkens K, Leary A, Luxenberg D . Human GM-CSF: molecular cloning of the complementary DNA and purification of the natural and recombinant proteins. Science. 1985; 228(4701):810-5. DOI: 10.1126/science.3923623. View

Saitoh Y, Mori H, Matsumoto K, Ushio Y, Hayakawa T, Mori S . Accumulation of amyloid in pituitary adenomas. Acta Neuropathol. 1985; 68(2):87-92. DOI: 10.1007/BF00688628. View

Howard Jr C . Longitudinal studies on the development of diabetes in individual Macaca nigra. Diabetologia. 1986; 29(5):301-6. DOI: 10.1007/BF00452067. View

Westermark P, Wernstedt C, Wilander E, Hayden D, OBrien T, Johnson K . Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells. Proc Natl Acad Sci U S A. 1987; 84(11):3881-5. PMC: 304980. DOI: 10.1073/pnas.84.11.3881. View

Johnson K, OBrien T, Hayden D, Jordan K, Ghobrial H, Mahoney W . Immunolocalization of islet amyloid polypeptide (IAPP) in pancreatic beta cells by means of peroxidase-antiperoxidase (PAP) and protein A-gold techniques. Am J Pathol. 1988; 130(1):1-8. PMC: 1880548. View

10.

Kaufman R, Davies M, Pathak V, Hershey J . The phosphorylation state of eucaryotic initiation factor 2 alters translational efficiency of specific mRNAs. Mol Cell Biol. 1989; 9(3):946-58. PMC: 362683. DOI: 10.1128/mcb.9.3.946-958.1989. View

11.

Betsholtz C, Svensson V, Rorsman F, Engstrom U, Westermark G, Wilander E . Islet amyloid polypeptide (IAPP):cDNA cloning and identification of an amyloidogenic region associated with the species-specific occurrence of age-related diabetes mellitus. Exp Cell Res. 1989; 183(2):484-93. DOI: 10.1016/0014-4827(89)90407-2. View

12.

Wisniewski H, Wegiel J, Wang K, Kujawa M, Lach B . Ultrastructural studies of the cells forming amyloid fibers in classical plaques. Can J Neurol Sci. 1989; 16(4 Suppl):535-42. DOI: 10.1017/s0317167100029887. View

13.

McCracken A, Kruse K . Intracellular transport of rat serum albumin is altered by a genetically engineered deletion of the propeptide. J Biol Chem. 1989; 264(35):20843-6. View

14.

Levy E, Carman M, Power M, Lieberburg I, van Duinen S, BOTS G . Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type. Science. 1990; 248(4959):1124-6. DOI: 10.1126/science.2111584. View

15.

Blake M, Udelsman R, Feulner G, Norton D, Holbrook N . Stress-induced heat shock protein 70 expression in adrenal cortex: an adrenocorticotropic hormone-sensitive, age-dependent response. Proc Natl Acad Sci U S A. 1991; 88(21):9873-7. PMC: 52823. DOI: 10.1073/pnas.88.21.9873. View

16.

Askanas V, Engel W, Alvarez R . Light and electron microscopic localization of beta-amyloid protein in muscle biopsies of patients with inclusion-body myositis. Am J Pathol. 1992; 141(1):31-6. PMC: 1886568. View

17.

Denning G, Anderson M, Amara J, Marshall J, Smith A, Welsh M . Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive. Nature. 1992; 358(6389):761-4. DOI: 10.1038/358761a0. View

18.

Rocken C, Linke R, Saeger W . Immunohistology of islet amyloid polypeptide in diabetes mellitus: semi-quantitative studies in a post-mortem series. Virchows Arch A Pathol Anat Histopathol. 1992; 421(4):339-44. DOI: 10.1007/BF01660981. View

19.

Tsang W, Chan J . Amyloid-producing squamous cell carcinoma of the uterine cervix. Arch Pathol Lab Med. 1993; 117(2):199-201. View

20.

Udelsman R, Blake M, Stagg C, Li D, Putney D, Holbrook N . Vascular heat shock protein expression in response to stress. Endocrine and autonomic regulation of this age-dependent response. J Clin Invest. 1993; 91(2):465-73. PMC: 287957. DOI: 10.1172/JCI116224. View