Islet amyloidosis (IA) is the principal lesion in the endocrine pancreas of human beings with non-insulin-dependent diabetes mellitus (NIDDM) and in the similar forms of diabetes mellitus in domestic cats and macaques. As such, the delineation of the pathogenesis of this form of amyloidosis may be crucial to the understanding of the development and progression of NIDDM. Islet amyloid polypeptide (IAPP) is a recently discovered polypeptide that is the principal constituent of IA in human beings, cats, and macaques. IAPP is produced by the pancreatic beta-cells and is co-packaged with insulin in the beta-cell secretory vesicles. Immunohistochemical and physiologic evidence supports the notion that the beta-cells are heterogenous with respect to their relative contents of insulin and IAPP. Therefore, although IAPP is co-secreted with insulin in response to a variety of well-known insulin secretagogues, the molar ratio of these two proteins that is released from the islets may vary, depending upon the glucose concentration and prevailing metabolic milieu. IAPP is highly conserved among mammalian species and has about 45% homology to another neuropeptide, calcitonin gene-related peptide. IAPP is encoded by a single-copy gene located, in the human being, on chromosome 12. IAPP is expressed as a 93 (murine)-89 (human)-amino acid prepropolypeptide that is processed enzymatically, resulting in the removal of amino- and carboxy-terminal propeptide segments. The 20-29 region of the IAPP molecule is most important in the ability of IAPP to form amyloid fibrils. The role of IAPP and IA in the pathogenesis of human NIDDM and similar forms of diabetes mellitus in cats and macaques may involve several possible mechanisms, including 1) direct physical/chemical damage to beta-cells, resulting in necrosis and loss of functional islet tissue, 2) biologic activities of IAPP that oppose those of insulin or abnormally suppress insulin secretion, and 3) interference by IA deposits of passage of insulin out of beta-cells and/or entrance of glucose and other secretogogues into the islet. The roles of each of these possible mechanisms have yet to be demonstrated. In addition, the physiological significance of the apparent IAPP deficiency in both insulin-dependent diabetes mellitus and NIDDM is currently unknown.

Abnormal mammary gland growth is a side effect of progestin therapy in some cats. In this retrospective study, the nature and significance of morphologic changes in the mammary gland of 17 megestrol acetate (MA)-treated cats were compared to mammary lesions in 97 untreated cats. Fourteen out of 17 MA-treated cats had non-neoplastic mammary lesions including fibroepithelial hyperplasia (nine cats), lobular hyperplasia (three cats), and duct ectasia (two cats); whereas three MA-treated cats had mammary neoplasms including one adenoma and two carcinomas. Although MA has been causally linked to mammary cancer in cats, only mammary fibroepithelial hyperplasia was clearly associated with MA therapy in this study. Fibroepithelial hyperplasia occurred in older (average age 8.1 years) neutered male and female cats in the MA-treated group and in younger (average age 2.1 years) female cats in the untreated group. Morphologically, both intraductal and solid fibroepithelial growth patterns were seen. Intraductal fibroepithelial hyperplasia was further subdivided into papillary and circumferential types. An apparent greater association between MA therapy and the intraductal types of fibroepithelial hyperplasia was noted. Furthermore, it appears likely that mammary lobular hyperplasia also is linked to MA therapy. Possible mammatrophic effects of MA and other growth-promoting agents in the cat are discussed.

No abstract

No abstract

No abstract