Absence of islet Alpha cell function in pancreatectomized patients

Tiengo, Antonio; Bessioud, M; Valverde, Isabel; Tabbi-Anneni, A.; DelPrato, Stefano; Alexandre, J. H.; Assan, R

doi:10.1007/bf00253865

Cited by 29 publications

(9 citation statements)

References 36 publications

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“…Diabetes secondary to total pancreatectomy has been proposed as a model of 'aglucagonaemic diabetes' [29], even though glucagon immunoreactivity is found in these patients [30][31][32][33][34]. Immunoreactive glucagon was higher in our patients, probably reflecting the non-specificity of 30K antibody [24][25] reacting with intestinal glucagon-like substances, which are increased after pancreatectomy [35].…”

Section: Discussionmentioning

confidence: 52%

Effect of insulin replacement on intermediary metabolism in diabetes secondary to pancreatectomy

et al. 1983

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Patients with diabetes due to pancreatectomy have metabolic features different from Type 1 (insulin-dependent) diabetes after insulin withdrawal. Whether or not glucagon by itself or combined glucagon-insulin absence are responsible for this metabolic behaviour is unknown. This study was carried out to evaluate the ability of insulin replacement to abolish differences between patients with Type 1 diabetes and patients with diabetes due to pancreatectomy. We studied the diurnal patterns of intermediary metabolites, free insulin, and glucagon using the Biostator (glucose-controlled insulin infusion system) and intensive subcutaneous insulin therapy in five patients after total pancreatectomy, five after partial pancreatectomy and seven patients with Type 1 diabetes. All were studied for 24 h after an overnight period of normoglycaemia. Insulin requirement was lower in the patients with total pancreatectomy than in patients with partial pancreatectomy or Type 1 diabetes during both types of insulin treatment (p less than 0.05). Blood glucose and free insulin were similar in all the groups in both conditions. Immunoreactive glucagon was higher in the patients with diabetes secondary to pancreatectomy than in Type 1 diabetic patients. However, glucagon levels did not increase after arginine infusion in the patients with total pancreatectomy, and column chromatography of blood samples from two totally pancreatectomized patients showed no significant levels of immunoreactive pancreatic glucagon. Non-esterified fatty acids and ketone bodies were similar during Biostator and intensive subcutaneous insulin therapy. By contrast, gluconeogenic precursors (lactate, pyruvate, alanine and glycerol) were higher in patients with total pancreatectomy than in patients with partial pancreatectomy and Type 1 diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 52%

Effect of insulin replacement on intermediary metabolism in diabetes secondary to pancreatectomy

et al. 1983

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“…That is not a new finding (4 -6). Assuming comparable suppression of ␤-cell insulin and ␣-cell glucagon secretion by octreotide, it suggests that the antibody used to measure glucagon recognizes species in addition to biologically active 3,500-Da glucagon, a phenomenon well documented with earlier antibodies (e.g., [25][26][27][28][29]. Clearly, however, given lower rates of glucose production and plasma glucose concentrations during octreotide infusion with insulin replacement, octreotide produced biological glucagon deficiency.…”

Section: Discussionmentioning

confidence: 96%

“…Thus, in the short-term, factors in addition to these hormones must be involved in maintenance of the postabsorptive glucose level. Nonetheless, chronic insulin and glucagon deficiencies (e.g., in pancreatectomized humans who have low insulin levels and little or no circulating biologically active 3,500-Da glucagon [25][26][27][28][29]) cause diabetes. That indicates that among the pancreatic islet hormones, insulin plays a predominant role in maintenance of the postabsorptive plasma glucose concentration and further that elevated glucagon levels are not a requisite condition for the development of diabetes.…”

Section: Discussionmentioning

confidence: 99%

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Glucagon, in Concert With Insulin, Supports the Postabsorptive Plasma Glucose Concentration in Humans

et al. 2007

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OBJECTIVE-Given the interest in glucagon antagonism as a potential treatment of diabetes, we tested the hypothesis that glucagon, in concert with insulin, supports the postabsorptive plasma glucose concentration in humans.RESEARCH DESIGN AND METHODS-Following preliminary studies that indicated that a peripheral intravenous insulin dose of 0.1 mU ⅐ kg Ϫ1 ⅐ min Ϫ1 (lower than those used previously) provides basal insulin replacement and that a glucagon dose of 1.0 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 underreplaces basal glucagon, we infused the somatostatin analog octreotide (30 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 ) (with growth hormone replacement) over 4 h in 14 healthy adults on four separate occasions to produce endogenous insulin and glucagon deficiency with 1) saline (combined insulin and glucagon deficiency), 2) insulin replacement (isolated glucagon deficiency), 3) partial glucagon replacement (insulin and partial glucagon deficiency), and 4) insulin and partial glucagon replacement (partial glucagon deficiency).RESULTS-During combined insulin and glucagon deficiency, glucose production decreased and then increased, and mean (ϮSE) plasma glucose decreased from 83 Ϯ 1 to 63 Ϯ 2 mg/dl at 60 min and then increased to 89 Ϯ 3 mg/dl at 240 min. During isolated glucagon deficiency, plasma glucose decreased to hypoglycemic levels and was 55 Ϯ 2 mg/dl at 240 min (P Ͻ 0.0001 vs. combined insulin and glucagon deficiency). Partial glucagon replacement raised plasma glucose to higher levels (P ϭ 0.0469) during insulin deficiency and to higher levels (P ϭ 0.0090) during insulin replacement.CONCLUSIONS-These three findings provide direct evidence that glucagon, in concert with insulin, supports the postabsorptive plasma glucose concentration in humans.

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“…True glucagon was localized exclusively in the stomach because pancreatectomy plus gastrectomy virtually removed glucagon from plasma (134). In contrast to dogs, in totally depancreatized humans, there is only a negligible amount of plasma glucagon (9,20,87,135,179). We and others who detected glucagon-like peptides in the brain (80,177,181) stimulated interest in this field.…”

Section: Resolving the Controversy Regarding The Existence Of Extrapamentioning

confidence: 99%

Odyssey between Scylla and Charybdis through storms of carbohydrate metabolism and diabetes: a career retrospective

Vranić

2010

American Journal of Physiology-Endocrinology and Metabolism

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Vranic M. Odyssey between Scylla and Charybdis through storms of carbohydrate metabolism and diabetes: a career retrospective. Am J Physiol Endocrinol Metab 299: E849 -E867, 2010. First published September 7, 2010; doi:10.1152/ajpendo.00344.2010.-This research perspective allows me to summarize some of my work completed over 50 years, and it is organized in seven sections. 1) The treatment of diabetes concentrates on the liver and/or the periphery. We quantified hormonal and metabolic interactions involved in physiology and the pathogenesis of diabetes by developing tracer methods to separate the effects of diabetes on both. We collaborated in the first tracer clinical studies on insulin resistance, hypertriglyceridemia, and the Cori cycle.2) Diabetes reflects insulin deficiency and glucagon abundance. Extrapancreatic glucagon changed the prevailing dogma and permitted precise exploration of the roles of insulin and glucagon in physiology and diabetes. 3) We established the critical role of glucagon-insulin interaction and the control of glucose metabolism during moderate exercise and of catecholamines during strenuous exercise. Deficiencies of the release and effects of these hormones were quantified in diabetes. We also revealed how acute and chronic hyperglycemia affects the expression of GLUT2 gene and protein in diabetes. 4) We outlined molecular and physiological mechanisms whereby exercise training and repetitive neurogenic stress can prevent diabetes in ZDF rats. 5) We and others established that the indirect effect of insulin plays an important role in the regulation of glucose production in dogs. We confirmed this effect in humans and demonstrated that in type 2 diabetes it is mainly the indirect effect. 6) We indicated that the muscle and the liver protected against glucose changes. 7) We described molecular mechanisms responsible for increased HPA axis in diabetes and for the diminished responses of HPA axis, catecholamines, and glucagon to hypoglycemia. We proposed a new approach to decrease the threat of hypoglycemia. exercise; stress; diabetes pathogenesis; hypoglycemia SCYLLA AND CHARYBDIS are two sea monsters in Greek mythology described by Homer. They were located close enough to each other that they posed an inescapable threat to passing sailors, including Odysseus. Avoiding Charybdis meant passing too close to Scylla and vice versa. Substitute Scylla for granting agencies and Charybdis for high-impact journals. There is a feedback relationship between problems with granting agencies and the acceptance of papers in important journals. The storms (originality) require the strength of Odysseus to sail safely toward acceptance of a new and original hypothesis.I am very indebted to Amira Klip (the first non-U.S. editor of the American Journal of Physiology -Endocrinology and Metabolism), who invited me to write a review related to my research endeavors over the past half-century. Since this is a personal history rather than a general review, I have focused primarily on my laboratory work as well ...

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Absence of islet Alpha cell function in pancreatectomized patients

Cited by 29 publications

References 36 publications

Effect of insulin replacement on intermediary metabolism in diabetes secondary to pancreatectomy

Effect of insulin replacement on intermediary metabolism in diabetes secondary to pancreatectomy

Glucagon, in Concert With Insulin, Supports the Postabsorptive Plasma Glucose Concentration in Humans

Odyssey between Scylla and Charybdis through storms of carbohydrate metabolism and diabetes: a career retrospective

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