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Query: UMLS:C0011849 (diabetes)
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A 53 year old woman presented with diabetes mellitus, hyperglucagonemia (600 to 1,500 pg/ml), clinical hyperparathyroidism and an abdominal mass diagnosed on biopsy as an islet cell carcinoma. Glucagon content of the tumor was 0.78 mug/g wet weight. Hourly blood samples during a 24 hour period revealed a direct correlation between plasma glucose and glucagon. The oral administration of glucose paradoxically increased whereas the intravenous administration decreased plasma glucagon. Circulating glucagon levels were markedly increased with arginine and epinephrine infusion. Both short- and long-term administration of alpha adrenergic blockade depressed the glucagon response to epinephrine infusion. In contrast, long-term alpha adrenergic blockade increased glucagon secretion despite improved glucose tolerance during a second 24 hour study. Although the patient demonstrated overt clinical and chemical findings of hyperparathyroidism, parathyroid hormone (PTH) was not detected in her plasma. The pattern of tumor growth was consistent with an origin from pancreatic islets. We conclude that (1) the tumor was responsive to physiologic stimuli known to affect glucagon secretion; (2) elevations of plasma glucagon levels with oral and dietary glucose suggest regulation of secretion by intestinal factors; and (3) improvement of glucose tolerance with alpha adrenergic blockade may be related to increased insulin secretion.
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PMID:Uncontrolled diabetes mellitus and hyperglucagonemia associated with an islet cell carcinoma. 4 4

Described here is a patient who had an islet cell carcinoma containing both glucagon (glucagonoma) and insulin (insulinoma). Complete removal of the tumor was possible. Immunoreactive glucagon (IRG) could be extracted from all parts of the tumor (approximately 50 mug./gm.) and was shown to be fully bioactive. Immunoreactive insulin (IRI) could be extracted only from one section of the tumor (approximately 30 mug./gm.). The clinical and biochemical manifestations of the disease were dermatitis, diabetes, weight loss, anemia, hypoaminoacidemia, and hyperketonemia. The diabetes was characterized by low or normal fasting blood glucose concentrations and by impaired glucose tolerance (Kg = 0.4). After complete removal of the tumor, the dermatitis cleared, the catabolic state changed into an anabolic state, blood amino acid concentrations increased, and blood ketone-body concentrations decreased. Fasting blood glucose concentrations, however, rose above 200 mg./dl., and glucose tolerance declined further (Kg = 0.15). Hourly blood sampling for 24 hours, intravenous and oral glucose tolerance tests, intravenous arginine and tolbutamide tolerance tests with serial determinations of IRG, IRI, and blood glucose were performed preoperatively and again two weeks and two months postoperatively. The results of these studies demonstrated marked abnormalities in the stimulation and suppression of glucagon and insulin release. In addition, they failed to demonstrate a glycemic effect on the chronically elevated glucagon concentrations in this patient, while identifying insulin as the dominant factor determining blood glucose homeostasis.
Diabetes 1977 Feb
PMID:An islet cell carcinoma containing glucagon and insulin. Chronic glucagon excess and glucose homeostasis. 19 71

A patient with functioning islet cell carcinoma is described who had amelioration of her hypoglycemia during the development of ectopic ACTH syndrome. Moon facies and hyperkalemic metabolic acidosis were also present in this patient, features uncommonly seen in the actopic ACTH syndrome. At autopsy, she was found to have active tuberculosis. Prophylactic antituberculous therapy should be given to high-risk patients with the ectopic ACTH syndrome. High doses of ACTH may be palliative in refractory hypoglycemic states.
Diabetes 1975 Jun
PMID:Amelioration of hypoglycemia in a patient with malignant insulinoma during the development of the ectopic ACTH syndrome. 23

Human C-peptide is determined by radioimmunoassay. On gel filtration of serum from a healthy subject and from a patient with islet cell carcinoma, C-peptide (MW 3025) appears ahead of insulin (MW 5808) and shows much higher molar concentrations than the hormone. Human proinsulin cross-reacts with our antiserum to synthetic human C-peptide. On direct determination of immunomeasurable C-peptide (IMCP) in fasting serum of 25 healthy subjects we find an average of 1.8 (+/- 0.4) ng/ml, corresponding to 60.4 X 10(-11) Mol/l. The molar concentration is about five-fold as compared to IMI (immuno-measurable insulin). IMCP and IMI patterns are not identical on stimulation of beta-cell secretion in healthy subjects by i.v. glucose or glucose-glibenclamide. This is probably due to differences in peripheral metabolism of both compounds. We conclude from our results that C-peptide determined in peripheral venous serum is a better indicator of beta-cell secretion than is insulin. Among 26 insulin-treated juvenile diabetics 15 show not measurable and 11 subnormal IMCP levels in fasting serum. No rise in IMCP is found 1-2 h following breakfast. Four juvenile patients receiving no insulin in a phase of total diabetes remission have normal or raised fasting IMCP concentrations. Only 2 out of 24 adult diabetics (16 treated with insulin and 8 with tablets) show non-measurable fasting IMCP concentrations, in another 4 patients values are below and in the remaining 18 cases above 1 ng/ml serum. Stimulation of beta-cell secretion through glucose-glibenclamide is more or less impaired in all adult diabetics compared to the healthy subjects.
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PMID:Human C-peptide. Part II: Clinical studies. 82 96

Pancreatojejunal anastomosis disruption still represents the main postoperative complication after pancreatoduodenectomy. In this study, a technique of occlusion of the residual pancreatic stump instead of pancreatojejunal anastomosis is proposed. Between March, 1981 and August, 1987, we performed 51 pancreatoduodenectomies, using Neoprene injection in the Wirsung duct, for carcinoma of the pancreatic head (28 cases), ampullary carcinoma (12 cases), islet cell carcinoma (5 cases), and chronic pancreatitis (6 cases). We observed a 33.3% overall morbidity, with a 5.8% operative mortality. The complications observed seemed not to be related to the technique of pancreatic stump occlusion, except for 2 pancreatic fistulas which spontaneously resolved. Abdominal ultrasound and computed tomography scan performed during the follow-up did not show any significant morphological alteration of the residual stump. Pancreatic endocrine function was assessed in 10 patients by evaluating blood glucose, plasma insulin and plasma glucagon levels both fasting and after oral glucose, and intravenous arginine infusion. These tests were performed before surgery and 15 days, 6 months, 1, 2, and 3 years after surgery. The results showed that 60% of the patients had impaired glucose tolerance before surgery and the percentage did not significantly change up to 3 years later (75%). No patient developed diabetes mellitus, and only 1 patient progressed from a normal to an impaired glucose tolerance. In conclusion, intraductal injection of Neoprene after pancreatoduodenectomy seems to be a safer procedure compared to pancreatojejunal anastomosis and does not induce a post-surgical diabetes.
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PMID:Pancreatoduodenectomy with occlusion of the residual stump by Neoprene injection. 254 44

A 56-year-old woman with many unusual manifestations of von Hippel-Lindau syndrome is described. In addition to retinal hemangioblastomas, pheochromocytoma, renal cell carcinoma, and multiple organ cysts, she had a cerebellar astrocytoma, pancreatic exocrine insufficiency, diabetes mellitus, thyrotoxicosis, and a metastatic calcitonin-secreting islet cell carcinoma. This case report documents the first example of a metastatic islet cell tumor in a patient with von Hippel-Lindau disease. The possible relationship between this disorder, the other neurocutaneous syndromes, and the multiple endocrine neoplasia syndromes is discussed.
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PMID:Metastatic islet cell tumor in von Hippel-Lindau disease. 633 Nov 59

The incidence of pancreatic cancer has increased recently. The average age of pancreatic cancer patients in our series was 60.6 years; the male to female ratio was 2.3:1. As for tumor location, the head (45.5%) was the most frequent followed by the body (32.7%) and the tail (20%). Pancreatic cancers were histologically classified as duct carcinoma (88.2%), acinar cell carcinoma (0.9%), islet cell carcinoma (1.8%) and undifferentiated carcinoma (9.1%). In 17 cases (15.5%), diabetes mellitus was an accompanying complication.
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PMID:[Evaluation of autopsy cases in pancreatic cancer]. 666 9

Somatostatinoma is one of the rarest tumours of the endocrine pancreas. Cardinal manifestations of a somatostatinoma include gallstones, mild diabetes mellitus, steatorrhoea, diarrhoea and dyspepsia. Like any other pancreatic islet cell carcinoma, a somatostatinoma may also produce several different hormones such as adrenocorticotropic hormone, calcitonin, vasoactive intestinal polypeptide, pancreatic polypeptide, gastrin, insulin, and glucagon. In many cases, the clinical picture is dominated by the effect of these other hormones. We present a patient with somatostatinoma in which an immunocytochemical study of the specimens from pancreas and liver showed a weak positive reaction for gastrin besides a strong positive reaction for somatostatin. Interestingly, this patient also showed the signs of carcinoid syndrome which was successfully treated with octreotide.
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PMID:Carcinoid syndrome due to a malignant somatostatinoma. 749 79

Pancreatoduodenectomy and extended distal pancreatectomy for benign tumors in the pancreatic neck and body incur a notable waste of normal tissue and unnecessary risk of both diabetes mellitus and splenic loss. We describe the technique of a limited resection of the middle portion of the pancreas, termed middle segment pancreatectomy, and report our results in 12 patients. Middle segment pancreatectomy was used in 12 consecutive patients with pancreatic tumors of the neck or body. The transected pancreatic head was sutured with duct ligation, and a Roux-en-Y loop of jejunum was anastomosed to the tail using mucosa-to-mucosa duct approximation and a 5F catheter for duct stenting and drainage. In 12 patients, 7 with cystic tumors (5 patients with serous cystadenoma; 2 patients with mucinous cystic neoplasms), 3 with islet cell adenomas, 1 with islet cell carcinoma, and 1 with intraductal papillary mucinous tumor, the tumor was resected by a middle segment pancreatectomy. In each case, the tumor, measuring 0.9 to 5.2 cm, lay in the neck or body of the pancreas and could not be safely enucleated without compromising the pancreatic duct. Each tumor was resected with clear margins. Two patients had a temporary pancreatic fistula; 1 patient had delayed gastric emptying. Median postoperative length of stay was 8 days. No patient became diabetic or required oral pancreatic enzyme supplements. No local recurrences occurred after a mean follow-up of 18 months. Middle segment pancreatectomy is a safe and effective technique for resecting selected pancreatic tumors in the neck and body of the pancreas while preserving pancreatic endocrine and exocrine function and the spleen.
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PMID:Middle segment pancreatectomy: a novel technique for conserving pancreatic tissue. 951 49

Apoptosis, the process of programmed cell death, plays a critical role in many normal and pathological (disease) processes. In normal tissues, apoptosis functions in the homeostatic maintenance of proper tissue and organ size by eliminating aged cells to offset the birth of new cells that arise by mitosis. In disease, apoptosis can affect the pathological process is two disparate ways. There are diseases that have too much apoptosis such as autoimmune diabetes and Alzheimer's, or those that have too little apoptosis, such as cancer. This review will focus on the latter and, more specifically, detail and summarize some important lessons learned about apoptosis and cancer from studying a transgenic mouse model of islet cell carcinoma, RIP-Tag, as outlined below.
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PMID:Tumor cells utilize multiple pathways to down-modulate apoptosis. Lessons from a mouse model of islet cell carcinogenesis. 1066 71


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