Glucagon Immunoreactivities and Amino Acid Profile in Plasma of Duodenopancreatectomized Patients

Müller, W.; Berger, Michael; Suter, Peter M.; Cüppers, H J; Reiter, J.; Wyss, Thomas R.; Berchtold, Peter; Schmidt, Felix; Assal, J. P.; Renold, Albert E.

doi:10.1172/jci109381

Cited by 46 publications

(31 citation statements)

References 42 publications

(48 reference statements)

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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: 97%

“…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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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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

et al. 2007

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“…Thus, in patients with pancreatic diabetes, System A amino acids and gluconeogenic amino acids showed higher values than those in patients with primary diabetes, and their amino acid profile resembled that in diabetic patients with total pancreatectomy (Boden et al 1974;Muller et al 1979). Furthermore, we studied the correlation between plasma glucagon and plasma amino acids as the factors possibly contributing to changes in amino acid level.…”

Section: Discussionmentioning

confidence: 98%

“…It has been established that the plasma glucagon level becomes abnormally low in patients with total pancreatectomy (Muller et al 1974). In this case, plasma levels of gluconeogenic amino acids such as Ala and Ser and ureagenetic amino acids such as Orn and Arg increase (Muller et al 1979). It has been reported that plasma amino acid levels in such cases would tend to normalize after the administration of glucagon (Boden et al 1974).…”

Section: Discussionmentioning

confidence: 99%

“…Although it has been reported that hypoglucagonemia due to total pancreatectomy does influence the profile of plasma amino acids (Boden et al 1974;Muller et al 1974Muller et al , 1979Muller et al 1983), it is conceivable that in these patients the food consumption (especially protein consumption) is low. In addition, patients with total pancreatectomy vary in their food passing process depending on the method of pancreatectomy.…”

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confidence: 99%

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Increased Plasma Gluconeogenic and System A Amino Acids in Patients with Pancreatic Diabetes due to Chronic Pancreatitis in Comparison with Primary Diabetes.

Nakamura

Takebe

Kudoh

et al. 1994

Tohoku J. Exp. Med.

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We examined the plasma amino acid profiles of 17 patients with pancreatic diabetes in comparison with those of 14 healthy subjects and 16 patients with primary diabetes of similarly poor glycemic control. We also measured fasting plasma glucagon and free insulin levels in patients with pancreatic diabetes and in those with primary diabetes. The fasting plasma amino acid level was highest in patients with pancreatic diabetes. Furthermore, the plasma glucagon level in patients with pancreatic diabetes was significantly low, and negative correlations were found between glucagon and glucagon-related System A and gluconeogenic amino acids. On the other hand, the levels of branched-chain amino acids (BCAA) and System L amino acids, which are subjected to change in the state of diabetes mellitus, increased in patients with pancreatic diabetes. From the above results, we determined that the amino acid profile in patients with pancreatic diabetes resembled that in patients with total pancreatectomy. It is our opinion that the increases of amino acid levels (gluconeogenic and System A amino acids) in patients with pancreatic diabetes is not dependent on maldigestion/malabsorption under treatment, but is mainly dependent on glucagon deficiency. gluconeogenic and system A amino acids; pancreatic diabetes; hypoglucagonemia With regard to the relationship between amino acid metabolism and chronic pancreatitis, the following three points can be considered; 1) Abnormalities of amino acids as a cause of hereditary familial pancreatitis among chronic pancreatitis sufferers (Gross et al. 1957), 2) possible change in plasma amino acid profile due to malnutrition caused by maldigestion resulting from chronic pancreatitis and 3) abnormal amino acid metabolism due to secondary diabetes

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Diabetes Secondary to Acquired Disease to the Pancreas

Prato¹,

Coppelli²,

Tiengo³

2004

International Textbook of Diabetes Mellitus

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Secondary diabetes is a condition of hyperglycemia which develops after the destruction of the pancreatic tissue by an acquired disease with subsequent impairment of exocrine and endocrine pancreatic functions. In general, any pathologic process of the pancreatic acinar tissue may results in an insult to its endocrine component, leading to some degree of hormone insufficiency. This condition was first described in 1788 by Sir Thomas Cawley, but it was soon appreciated that hyperglycemia can ensues acute and chronic pancreatitis, partial and total pancreatectomy, neoplasia as well as systemic processes involving the pancreas, such as hemochromatosis and cystic fibrosis. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus of the American Diabetes Association has identified these forms of diabetes as “diabetes secondary to diseases of the exocrine pancreas.” The new diagnostic criteria for diabetes introduced by the ADA and WHO Expert Committees are likely to influence the prevalence of diabetes in patients with diseases of the exocrine pancreas, but direct assessment using the new criteria is still too scanty. When the 1979 NDDG and 1985 WHO criteria are used, it can be calculated that diabetes secondary to disease of the exocrine pancreas represents, approximately, 0.5% of all cases of diabetes mellitus. Its frequency is likely to be twice as high in populations with heavy alcohol consumption. In the tropics, the prevalence of diabetes secondary to fibrocalculous pancreatitis can be as high as 10–20%. At variance with the selective B‐cell destruction occurring in type 1 diabetes, pancreatic diabetes is characterized by concomitant destruction of all endocrine cells of the islet of Langherans. The dual insulin–glucagon deficit is responsible for many of the metabolic and clinical manifestation of this form of diabetes, including lower risk for ketoacidosis and more frequent and severe hypoglycemic episodes. Since the late 1950s, the general idea has been that secondary diabetes was not associated with vascular complications. However, with the improved life expectancy of these patients during the past few years, a similar prevalence of retinopathy and microalbuminuria has been described in pancreatic and type 1 diabetes mellitus. The knowledge of the hormonal, metabolic, and clinical features of these forms of diabetes is essential in defining the most appropriate therapeutic strategies.

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Glucagon Immunoreactivities and Amino Acid Profile in Plasma of Duodenopancreatectomized Patients

Cited by 46 publications

References 42 publications

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

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

Increased Plasma Gluconeogenic and System A Amino Acids in Patients with Pancreatic Diabetes due to Chronic Pancreatitis in Comparison with Primary Diabetes.

Diabetes Secondary to Acquired Disease to the Pancreas

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