Islet amyloid polypeptide and insulin expression are controlled differently in primary and transformed islet cells

TY - JOUR

T1 - Islet amyloid polypeptide and insulin expression are controlled differently in primary and transformed islet cells

AU - Madsen, O D

AU - Michelsen, Bo Thomas

AU - Westermark, P

AU - Betsholtz, C

AU - Nishi, M

AU - Steiner, D F

AU - Nielsen, Jens Høiriis

PY - 1991/1

Y1 - 1991/1

N2 - The pancreatic beta-cell is a major site of islet amyloid polypeptide (IAPP) biosynthesis, and the peptide is coreleased with insulin. We have analyzed the expression of IAPP (mRNA and protein) in various cell types in normal and transformed murine islet cell cultures by Northern blot analyses and immunocytochemistry. IAPP is primarily coexpressed with insulin in the beta-cell of GH-promoted primary rat islet cell cultures. Additionally, a small population of non-beta-cells exhibited a prominent IAPP expression, and double staining experiments showed colocalization with glucagon or somatostatin in some of these cells. IAPP mRNA was confined to the beta-cell phenotype when analyzing the phenotypically stable in vivo tumor lines, MSL-G2-IN (insulinoma) and MSL-G-AN (glucagonoma), and the transgenic mouse islet cell lines, beta-Tc and alpha-Tc. However, IAPP and insulin expression were completely uncoupled in unstable heterogeneous clones such as NHI-6F. This clone is composed of primarily glucagon-producing cells in vitro, but insulin gene expression becomes dominant after passage in vivo. Interestingly, IAPP was hyperexpressed with glucagon under in vitro conditions in this clone. We conclude that the tissue specificity of expressions of IAPP and insulin are controlled differently, and that coexpression of IAPP with hormones different from insulin may be a marker for pluripotent transformed rat islet cell clones, which are able to activate insulin gene transcription during passage in vivo.

AB - The pancreatic beta-cell is a major site of islet amyloid polypeptide (IAPP) biosynthesis, and the peptide is coreleased with insulin. We have analyzed the expression of IAPP (mRNA and protein) in various cell types in normal and transformed murine islet cell cultures by Northern blot analyses and immunocytochemistry. IAPP is primarily coexpressed with insulin in the beta-cell of GH-promoted primary rat islet cell cultures. Additionally, a small population of non-beta-cells exhibited a prominent IAPP expression, and double staining experiments showed colocalization with glucagon or somatostatin in some of these cells. IAPP mRNA was confined to the beta-cell phenotype when analyzing the phenotypically stable in vivo tumor lines, MSL-G2-IN (insulinoma) and MSL-G-AN (glucagonoma), and the transgenic mouse islet cell lines, beta-Tc and alpha-Tc. However, IAPP and insulin expression were completely uncoupled in unstable heterogeneous clones such as NHI-6F. This clone is composed of primarily glucagon-producing cells in vitro, but insulin gene expression becomes dominant after passage in vivo. Interestingly, IAPP was hyperexpressed with glucagon under in vitro conditions in this clone. We conclude that the tissue specificity of expressions of IAPP and insulin are controlled differently, and that coexpression of IAPP with hormones different from insulin may be a marker for pluripotent transformed rat islet cell clones, which are able to activate insulin gene transcription during passage in vivo.

KW - Amyloid

KW - Animals

KW - Animals, Newborn

KW - Cell Line

KW - Cell Line, Transformed

KW - Gene Expression Regulation

KW - Glucagon

KW - Glucagonoma

KW - Growth Hormone

KW - Humans

KW - Immunohistochemistry

KW - Insulin

KW - Insulinoma

KW - Islet Amyloid Polypeptide

KW - Islets of Langerhans

KW - Mice

KW - Pancreatic Neoplasms

KW - RNA, Messenger

KW - Rats

KW - Simian virus 40

KW - Transfection

M3 - Journal article

C2 - 1850107

SN - 0888-8809

VL - 5

SP - 143

EP - 148

JO - Molecular endocrinology (Baltimore, Md.)

JF - Molecular endocrinology (Baltimore, Md.)

IS - 1

ER -