Regulation of insulin and glucagon secretion from a human islet cell adenoma. 1977

A J Bone, and R W Gumpert, and S L Howell, and J Sheldon, and M Tellez-Yudilevich, and M Tyhurst, and P G Whittaker, and F Zaheer

The regulation of insulin biosynthesis, and insulin and glucagon secretion have been investigated in a human islet cell adenoma, by incubation of tumour fragments. Both biosynthesis and secretion of insulin were strongly stimulated by incubation of islet tumour cells in the presence of increasing glucose concentrations in the range 2-8 mmol/1. However, 20 mM-glucose or 20 mM-glucose plus isobutyl methylxanthine (IBMX), both of which provide potent secretagogues for normal B cells, failed to stimulate proinsulin biosynthesis and secretion from the tumour cells. Overall rates of secretion, expressed as a proportion of total insulin content, were up to 20-fold higher than those expected for normal pancreatic tissue. Glucagon secretion from the tumour was stimulated by low glucose concentrations; normal A cells also respond in this way under these conditions. However, no stimulation of glucagon secretion occurred in the presence of IBMX. There was therefore a major alteration in the regulation both of insulin and glucagon secretion, in that release of neither hormone was stimulated by cyclic AMP. Ultrastructural examination showed the tumour to be rather heterogeneous. A and B cells with normal storage granule content and structure were seen, as well as a rather larger number of B cells containing some granules of atypical appearance. The insulin content of the tumour (13 i.u./g wet wt) was consistent with 6-8% of the tumour cells being B cells.

UI MeSH Term Description Entries
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D007516 Adenoma, Islet Cell A benign tumor of the pancreatic ISLET CELLS. Usually it involves the INSULIN-producing PANCREATIC BETA CELLS, as in INSULINOMA, resulting in HYPERINSULINISM. Islet Cell Tumor,Islet of Langerhans Tumor,Nesidioblastoma,Pancreatic Islet Cell Tumors,Island Cell Tumor,Adenomas, Islet Cell,Island Cell Tumors,Islet Cell Adenoma,Islet Cell Adenomas,Islet Cell Tumors,Langerhans Tumor Islet,Nesidioblastomas,Tumor Islet, Langerhans,Tumor, Island Cell,Tumor, Islet Cell,Tumors, Island Cell,Tumors, Islet Cell
D011384 Proinsulin A pancreatic polypeptide of about 110 amino acids, depending on the species, that is the precursor of insulin. Proinsulin, produced by the PANCREATIC BETA CELLS, is comprised sequentially of the N-terminal B-chain, the proteolytically removable connecting C-peptide, and the C-terminal A-chain. It also contains three disulfide bonds, two between A-chain and B-chain. After cleavage at two locations, insulin and C-peptide are the secreted products. Intact proinsulin with low bioactivity also is secreted in small amounts.
D005260 Female Females
D005934 Glucagon A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal GLUCAGON-LIKE PEPTIDES. Glucagon is secreted by PANCREATIC ALPHA CELLS and plays an important role in regulation of BLOOD GLUCOSE concentration, ketone metabolism, and several other biochemical and physiological processes. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1511) Glucagon (1-29),Glukagon,HG-Factor,Hyperglycemic-Glycogenolytic Factor,Proglucagon (33-61),HG Factor,Hyperglycemic Glycogenolytic Factor
D005947 Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000078790 Insulin Secretion Production and release of insulin from PANCREATIC BETA CELLS that primarily occurs in response to elevated BLOOD GLUCOSE levels. Secretion, Insulin
D000242 Cyclic AMP An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly

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