Somatostatin does not Cause Sustained Fasting Hyperglycemia in Man

Rizza, Robert A.; Verdonk, Carlos A.; Miles, John M.; Haymond, M. W.; Gerich, John

doi:10.1055/s-0028-1095806

Cited by 10 publications

(5 citation statements)

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“…Furthermore, a functional study on isolated human islet cells confirmed the importance of the sstr 5 receptor for insulin secretion (Zambre et al 1999). In studies on healthy human subjects, infusion of natural somatostatin results in a transient increase in glucose for about 6 h, despite a sustained suppression of insulin and glucagon (Rizza et al 1979).…”

Section: Discussionmentioning

confidence: 98%

Effects of somatostatin analogs on glucose homeostasis in rats

Schmid

Brueggen²

2011

Journal of Endocrinology

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Pasireotide (SOM230) is a multireceptor-targeted somatostatin analog with high binding affinity for sstr 1,2,3 and sstr 5 . The effects of pasireotide and octreotide on blood glucose, insulin, and glucagon levels in rats were evaluated alone and in combination. Single-dose s.c. pasireotide acutely elevated plasma glucose, whereas single-dose s.c. octreotide had no or a small hypoglycemic effect. Glucose elevation with s.c. pasireotide was transient with tachyphylaxis after repeated or continuous administration. Pasireotide and octreotide caused similar inhibitory effects on insulin secretion, whereas pasireotide had a weaker inhibitory effect on glucagon secretion than octreotide. Continuous infusion of pasireotide or injection of pasireotide long-acting release (LAR) resulted in only small and transient elevations of plasma glucose. Based on these results, and differences in the sstr binding affinity of pasireotide vs octreotide, it was hypothesized that the sstr 5 vs sstr 2 receptor activation ratio is the main driver of hyperglycemia after pasireotide. The results also suggest that stronger activation of sstr 2 may counteract the hyperglycemic effect. Indeed, co-administration of octreotide, which has a high affinity for sstr 2 , with a hyperglycemic dose of pasireotide did not cause significant changes in plasma glucose levels. In conclusion, although pasireotide and octreotide inhibited insulin to a similar degree, only pasireotide administration was associated with hyperglycemia. The strong glucagon inhibitory effect exhibited by octreotide but not pasireotide may explain this observation. The lack of hyperglycemia during co-administration of pasireotide and octreotide may be explained by the greater activation of sstr 2 compared with pasireotide alone, causing the insulinglucagon balance to shift within the normoglycemic range. Extrapolation of these data to humans must account for species differences in islet cell sstr expression.

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Section: Discussionmentioning

confidence: 98%

Effects of somatostatin analogs on glucose homeostasis in rats

Schmid

Brueggen²

2011

Journal of Endocrinology

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“…In these experiments, replacement glucagon doses of ~7 ng/kg-min resulted in glucagon plasma concentrations of ~40 to 60 pg/ml and relatively small increases in the glucagon infusion rates could result in a rise in blood glucose concentrations. 36,42,55 In addition, we rationalized that since subcutaneous insulin pump infusion was effective in controlling the plasma glucose 56-58 a similar argument could be made for glucagon.…”

Section: Mini-dose Glucagonmentioning

confidence: 99%

Minimizing Morbidity of Hypoglycemia in Diabetes

Chung

Haymond

2014

J Diabetes Sci Technol

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Type 1 diabetes is a common chronic disease of childhood and one of the most difficult conditions to manage. Advances in insulin formulations and insulin delivery devices have markedly improved the ability to achieve normal glucose homeostasis. However, hypoglycemia remains the primary limiting factor in achieving normoglycemia and is a frequent complication in children with acute gastroenteritis and/or poor oral intake. In situations of impaired carbohydrate intake or absorption, glucagon therapy is the only out-of-hospital treatment option available to families and caregivers. Glucagon is recommended for the treatment of severe hypoglycemia and rapidly increases blood glucose by increasing hepatic glucose production from glycogenolysis. Mini-dose glucagon is a widely utilized off-label treatment for managing mild or impending hypoglycemia and is administered as a small subcutaneous injection. It was initially described for use in children who were unable to tolerate or absorb oral carbohydrates but not in need of advanced medical care. Yet, mini-dose glucagon may be useful in any individual with relative insulin excess. The regimen aims to prevent severe hypoglycemic episodes and is safe, effective, and easily administered by patients and caregivers in the out-of-hospital setting. By empowering patients and their families, this important tool could help to alleviate the physical, psychosocial, and financial burden evolving from impending hypoglycemia.

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“…Indeed, although plasma glucose concentrations have been observed to increase above fasting levels during somatostatin infusion (5,6), a 12-h somatostatin infusion did not cause sustained fasting hyperglycemia (24). Thus, in the short-term, factors in addition to these hormones must be involved in maintenance of the postabsorptive glucose level.…”

Section: Discussionmentioning

confidence: 99%

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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Somatostatin does not Cause Sustained Fasting Hyperglycemia in Man

Cited by 10 publications

References 0 publications

Effects of somatostatin analogs on glucose homeostasis in rats

Effects of somatostatin analogs on glucose homeostasis in rats

Minimizing Morbidity of Hypoglycemia in Diabetes

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

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