Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fluctuations in blood glucose levels which occur in the brittle diabetic explain the difficulty of blood glucose control by insulin therapy as used at the present time. The artificial endocrine pancreas is a bedside device capable of maintaining blood sugar value within a normal range by the administration of adequate amounts of insulin or glucose given at the optimal time. The glycemic control of 11 brittle diabetics is improved during the 5 days after a 24 hour connection with the AEP. A better determination of adequate subcutaneous doses of insulin, based on the circadian insulin profile infused by the artificial endocrine pancreas, achieved the improvement of glycemia. Glucagon profile preceeding, during and after AEP is also discussed. Using a method of two injections daily of a mixture acterapid and semi-lente, as a general rule it is found that approximately fifty per cent of the dose must be given in the acterapid form. Glucagon value decreases during the 24 h artificial endocrine pancreas. This is suggestive of a possible role of hyperglucagonemia in brittle diabetes.
 ...
PMID:[Artificial pancreas: clinical and therapeutic value in 11 patients (author's transl)]. 38 66

Diabetes mellitus caused by pancreatic exocrine disease is a unique clinical and metabolic form of diabetes. The diagnosis of pancreatic diabetes caused by chronic pancreatitis may be elusive because it is occasionally painless and often not accompanied by clinical malabsorption until after hyperglycemia occurs. Diabetic patients with pancreatic calcification or clinically demonstrable pancreatic exocrine dysfunction will manifest the unique aspects of pancreatic diabetes described herein. Like other forms of diabetes, the primary hormonal abnormality in pancreatic diabetes is decreased insulin secretion. Patients with this disorder are unique in that they have low glucagon levels that respond abnormally to several physiological stimuli, blunted epinephrine responses to insulin-induced hypoglycemia, and malabsorption. In addition, they often have concomitant alcohol abuse with hepatic disease and poor nutrition. These characteristics result in increased levels of circulating gluconeogenic amino acids, decreased insulin requirements, a resistance to ketosis, low cholesterol levels, an increased risk of hypoglycemia while on insulin therapy, and the clinical impression of brittle diabetes. Retinopathy occurs at a rate equal to that of insulin-dependent diabetes but may be less severe in degree. Other complications of pancreatic diabetes have been less well studied but may be expected to be seen more frequently as these patients survive longer. The characteristics of pancreatic diabetes suggest that a conservative approach be taken in regard to intensive insulin therapy and tight blood glucose control.
 ...
PMID:Pancreatic diabetes mellitus. 269 11

A long-acting somatostatin analog, SMS 201-995, is now available to treat the hormonal manifestations of islet cell tumors. We report its use in a patient with a metastatic glucagonoma refractory to conventional therapy. This patient, who was severely disabled by the rash of necrolytic migratory erythema and brittle diabetes mellitus, allowed us to evaluate the therapeutic efficacy of SMS 201-995 and to gain insight into the origin of the rash. SMS 201-995 was administered subcutaneously (.05 mg twice a day). The rash improved markedly within 48 hours and was completely resolved within 1 week of treatment. Insulin requirements decreased from 90 U/day to zero during the first week of treatment. Corresponding to improvement in clinical symptoms circulating glucagon levels showed a marked decrease. There was no substantial change in plasma or urinary levels of zinc or in plasma amino acid levels. When SMS 201-995 was stopped, the rash recurred within 36 hours and it improved within 48 hours of readministration. The rash and diabetes have remained well controlled during 8 months of therapy but no change in tumor size has been seen on CT scan. The rapid changes in the rash related to the administration of SMS 201-995 indicate that the pathogenesis of necrolytic migratory erythema is probably due to circulating hyperglucagonemia or some other hormonal substance produced by the tumor.
 ...
PMID:Use of a somatostatin analog (SMS 201-995) in the glucagonoma syndrome. 287

Glucose counterregulation is the sum of processes that protect against development of hypoglycemia and that restore euglycemia if hypoglycemia should occur. In order of importance, the key counterregulatory factors are glucagon, epinephrine, growth hormone, cortisol, and hepatic autoregulation. These act primarily by increasing hepatic glucose output, initially via breakdown of glycogen and later by gluconeogenesis. In people without diabetes and in people with type II (non-insulin-dependent) diabetes, suppression of endogenous insulin secretion during hypoglycemia is also important in permitting full expression of the effects of counterregulation. People with diabetes are more prone to develop hypoglycemia for various reasons (e.g., insulin overdose, skipped meals, and intensive exercise); one that has recently been identified is impaired glucose counterregulation: patients with type I (insulin-dependent) diabetes (and to a lesser extent, patients with type II diabetes) lose the glucagon response to hypoglycemia; subsequent development of autonomic neuropathy with concomitant loss of the epinephrine response leads to almost complete paralysis of counterregulation and loss of recognition of hypoglycemia. To make matters worse, an episode of hypoglycemia that causes activation of counterregulation can lead to rebound hyperglycemia (Somogyi phenomenon); if this is improperly treated, brittle diabetes may follow. Thus, abnormalities in glucose counterregulation may predispose to severe hypoglycemia and prevent achievement of optimal glycemic control in patients with diabetes.
 ...
PMID:Lilly lecture 1988. Glucose counterregulation and its impact on diabetes mellitus. 305 59

Type 1 diabetes is an intrinsically unstable condition. However, the term "brittle diabetes" is reserved for those cases in which the instability, whatever its cause, results in disruption of life and often recurrent and/or prolonged hospitalization. It affects 3/1000 insulin-dependent diabetic patients, mainly young women. Its prognosis is poor with lower quality of life scores, more microvascular and pregnancy complications and shortened life expectancy. Three forms have been described: recurrent diabetic ketoacidosis, predominant hypoglycemic forms and mixed instability. Main causes of brittleness include malabsorption, certain drugs (alcohol, antipsychotics), defective insulin absorption or degradation, defect of hyperglycemic hormones especially glucocorticoid and glucagon, and above all delayed gastric emptying as a result of autonomic neuropathy. Psychosocial factors are very important and factitious brittleness may lead to a self-perpetuating condition. The assessment of brittle diabetes requires quantification of the variability of blood glucose levels. To quantify instability, measures which have been developed, include Mean Amplitude of the largest Glycemic Excursions (MAGE), Mean Of Daily Differences (MODD), Lability Index (LI), Low Blood Glucose Index (LBGI), Clarke's score, Hyposcore, and continuous blood glucose monitoring. Once psychogenic problems have been excluded, therapeutic strategies require firstly, the treatment of underlying organic causes of the brittleness whenever possible and secondly optimising standard insulin therapy using analogues, multiple injections and consideration of Continuous Subcutaneous Insulin Infusion. Alternative approaches may still be needed for the most severely affected patients. Isolated islet transplantation (IIT), which restores glucose sensing, should be considered in cases of hypoglycaemic unawareness and/or lability especially if the body mass index is < 25, but with current immunosuppressive protocols patients must have normal renal function and preferably no plans for pregnancy. Implantable pumps have advantages for patients who either weigh more than 80 kgs or have abnormalities of kidney or liver function or are highly sensitised.
 ...
PMID:Management strategies for brittle diabetes. 1707 32

Introduction: Pancreatic cancer is one of the most fatal cancers if not caught early and is associated with late disease presentation. Multifocal pancreatic cancer is particularly difficult to treat as cases that are amenable to surgical resection require total pancreatectomy. Such patients will develop brittle diabetes as they require exogenous insulin after surgery and in the apancreatic state lose counter-regulatory homeostatic mechanisms (i.e., glucagon). We present an elderly patient who underwent neoadjuvant chemotherapy and total pancreatectomy. The patient has adequate glycemic control postoperatively being managed with an insulin pump and remains disease free at 3 years and 3 months after resection. Case Presentation: A 72-year-old male presented with two tumors, in the head and tail of the pancreas, respectively, which were consistent with pancreatic adenocarcinoma by endoscopic ultrasound biopsy. Neoadjuvant FOLFIRINOX had been administered and total pancreatectomy was performed. The patient did well postoperatively and was discharged on postoperative day 8. The patient was seen by endocrinology pre- and postoperatively who started an insulin pump for glycemic management 2 weeks postoperatively. The patient's HbA1c was 7.9% at 3 months. The patient remains disease free at 3 years and 3 months with an HbA1c of 7.0% and a normal CA19-9. Conclusion: This case highlights that glycemic control after total pancreatectomy with the use of an insulin pump in the elderly population is achievable. Elderly patients can struggle with certain technologies and selecting appropriate patients for insulin pump therapy after total pancreatectomy is imperative.
 ...
PMID:Use of an Insulin Pump in the Elderly Surgical Patient: Tolerance of Total Pancreatectomy After Neoadjuvant Chemotherapy for Multifocal Pancreatic Cancer. 3078 60