Disease relevance of Glucagonoma

• Thus, with conversion to a neoplastic state, alpha cells of glucagonomas, much like beta cells of insulinomas, may secrete an increased amount of a larger, 9,000-mol wt glucagon species which may be a prohormone [1].
• All glucagonomas and nonfunctioning tumors were TTR immunoreactive, whereas gastrinomas and VIPomas were TTR negative [2].
• Reversal of a neurologic paraneoplastic syndrome with octreotide (Sandostatin) in a patient with glucagonoma [3].
• Study of patients with glucagonoma does suggest that glucagon has some role in the etiology of hyperglycemia in diabetic states; however, as in studies on diabetes, investigations on glucagonoma do not demonstrate that glucagon has a primary role in producing severe glucose intolerance [4].
• A marked reduction in symptoms, and in plasma glucagon and serum gastrin levels, was also observed in patients with glucagonoma and gastrinoma [5].

High impact information on Glucagonoma

• Cholecystokinin and glucagonoma [6].
• Treatment of inoperable glucagonoma with the long-acting somatostatin analogue SMS 201-995 [7].
• Basal immunoreactive glucagon was elevated in four of nine asymptomatic relatives of a patient with glucagonoma [8].
• Transplantable rat glucagonomas cause acute onset of severe anorexia and adipsia despite highly elevated NPY mRNA levels in the hypothalamic arcuate nucleus [9].
• Synthesis of T antigen in endocrine alpha cells results in the heritable development of pancreatic glucagonomas [10].

Chemical compound and disease context of Glucagonoma

• Successful treatment of metastatic glucagonoma with dacarbazine [11].
• Thus, alpha-TC glucagonoma cells contain ATP-sensitive K+ channels that regulate glucagon release, yet allow inhibition of hormone release by glucose [12].
• Metastatic glucagonoma: clinical response to a combination of 5-fluorouracil and alpha-interferon [13].
• Phenylalanine hydroxylation was moderately higher only in the male patient with glucagonoma (+ approximately 30%, delta >2 SD) [14].
• Therefore, we studied basal postabsorptive leucine, phenylalanine and tyrosine turnover following L-[D3]-Leucine, L-[D5]-Phenylalanine and L-[D2]-Tyrosine i.v. infusions in one male and one female patient with glucagonoma, compared with healthy control volunteers [14].

Biological context of Glucagonoma

• 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 [15].
• Problems with both glucose homeostasis and myocardial function could, therefore, theoretically be anticipated following resection of a glucagonoma [16].
• Amino acid, glucose, and lipid kinetics after palliative resection in a patient with glucagonoma syndrome [17].
• Forced expression of recombinant PDX1 in the glucagonoma resulted in efficient transcriptional activation of the endogenous insulin and IAPP genes, but did not affect glucagon gene activity [18].

Anatomical context of Glucagonoma

• Induction of insulin and islet amyloid polypeptide production in pancreatic islet glucagonoma cells by insulin promoter factor 1 [19].
• A pancreatic alpha-like cell line has been established from a glucagonoma arising in transgenic mice expressing a hybrid gene consisting of the rat glucagon-promoter sequence fused to the sequence encoding the SV40 T-antigen oncoprotein [20].
• Rarely, glucagonoma with massive destruction of the pancreas or other factors may induce severe glucose intolerance [4].
• We also demonstrate that c-Maf, another member of the Maf family of transcription factors, is expressed in islet alpha-cells and in a glucagonoma cell line (alphaTC1), but not in gamma- and delta-cells [21].
• The glucagonoma syndrome is characterized by elevated serum glucagon, a pancreatic alpha-cell tumor, anemia, hypoaminoacidemia, and necrolytic migratory erythema [22].

Gene context of Glucagonoma

• The glucagonomas also lose E-cadherin expression and instead express a cadherin which is similar to N-cadherin in brain [23].
• Whereas primary islet cells at all ages express unsialylated NCAM and E-cadherin, as do insulinomas, the glucagonomas express the polysialylated NCAM, which is characteristic for developing neurons [23].
• Noticeably, the proportion of glucagon-producing cells immunoreactive for PC3 was high in the gut and low in pancreatic islets and glucagonomas, whereas the reverse occurred for PC2 [24].
• A patient presenting clinically with the glucagonoma syndrome had high plasma glucagon levels (1920 ng/l) and at laparotomy, a pancreatic islet cell tumour was removed [25].
• Insulinomas, glucagonoma, PP-omas and non-functioning tumours were weakly stained for cdk6 and p16 [26].

Analytical, diagnostic and therapeutic context of Glucagonoma

• The glucagonoma cell line InR1G9 was transduced with a Pdx1-encoding lentiviral vector and insulin and glucagon mRNA levels were analysed by northern blot and real-time PCR [27].
• A newly developed, long-acting somatostatin analogue, SMS 201-995, which the patient can self-administer as a subcutaneous injection, has proven effective in suppressing glucagon secretion from glucagonomas and, in some cases, causing remission of clinical symptoms [28].
• Gel filtration of plasma from a patient with a clinical syndrome of glucagonoma and a total plasma glucagon level of 2600 pg/ml, revealed the four glucagon immunoreactive fractions found in normal subjects [29].
• Ghrelin expression was identified in a case of glucagonoma associated with multiple endocrine neoplasm type I both by Northern blot analysis using total RNA and by immunohistochemistry, although the plasma ghrelin level was not elevated [30].
• Neurologic involvement in glucagonoma syndrome: response to combination chemotherapy with 5-fluorouracil and streptozotocin [31].

References