Infusion of pramlintide, a human amylin analogue, delays gastric emptying in men with IDDM

Kong, Marie‐France; King, Paromita; Macdonald, I. A.; Stubbs, T. A.; Perkins, Alan C.; Blackshaw, P. E.; Moyses, Chris; Tattersall, R. B.

doi:10.1007/s001250050646

Cited by 121 publications

(96 citation statements)

References 25 publications

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“…This could possibly be due to a delay of emptying caused by endogenous amylin and/or insulin which will have been co-secreted in response to the glucose drink. Thus, subcutaneous injections of pramlintide cause retention of food in the proximal stomach, similar to an intravenous infusion of pramlintide [10]. This may be an extension of the effects of glucose described by Collins et al [22].…”

Section: Discussionmentioning

confidence: 67%

“…In a previous study we have shown that an intravenous infusion of pramlintide delayed gastric emptying in men with IDDM but the dose of pramlintide was supraphysiological in relation to the amylin response to food in non-diabetic subjects [10]. The purpose of this study was to examine the dose response effect of pramlintide on gastric emptying and to determine the duration of any effect by assessing whether administration of the drug before one meal has an impact on the subsequent meal.…”

Section: : 577±583]mentioning

confidence: 99%

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The effect of single doses of pramlintide on gastric emptying of two meals in men with IDDM

et al. 1998

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Gastric emptying is a significant determinant of the blood glucose response after an oral carbohydrate load [1] due to the key role this process plays in regulating the rate of nutrient delivery to the small intestine. Gastric emptying may therefore be a previously under-recognized contributor to variations in glycaemic control in diabetes mellitus. Faster rates of gastric emptying have been reported not only in rat models of insulin-dependent diabetes mellitus (IDDM) [2,3] but also in patients with IDDM [4,5] and recent studies suggest that modulation of gastric emptying could be used to improve glycaemic control in patients with diabetes [6].Amylin is a 37 amino acid polypeptide co-secreted with insulin by pancreatic beta cells, in response to nutrient stimuli. It circulates at concentrations of 5±30 pmol/l in normal subjects. IDDM patients are not only insulin deficient but also amylin deficient [7,8]. Amylin concentrations in IDDM patients range from the lower end of the normal range to undetectable and do not increase in response to a glucose load. The peptide pramlintide is a stable trisub- Diabetologia (1998) Summary In a previous study we have shown that an intravenous infusion of pramlintide (an analogue of human amylin) delayed gastric emptying, but the dose of pramlintide was supraphysiological in relation to the amylin response to food in non-diabetic subjects. The purpose of this study was to examine the dose response relationship of subcutaneous injections of pramlintide on gastric emptying and to determine whether administration of the drug before one meal has an impact on the subsequent meal. Eleven men with insulin-dependent diabetes mellitus were studied in a double-blind, randomised, four-way crossover design. None had autonomic neuropathy. Euglycaemia was maintained overnight before the study day. At 30 min the patients self-injected their usual morning insulin and at 15 min they injected the study drug (either placebo or 30, 60 or 90 mg pramlintide) subcutaneously. At 0 min they ate a standard meal consisting of a pancake, labelled with 99m Tc, and a milkshake containing 3-ortho-methylglucose (3-OMG). Gastric emptying images were obtained for the next 8 h. At 240 min the subjects ate a similar meal, but on this occasion the pancake was labelled with 111 In. All three doses of pramlintide delayed emptying of the solid component of the first meal (p < 0.004) with no significant difference between the drug doses. There were no differences between placebo and pramlintide after the second meal. All three doses of pramlintide resulted in a prolongation in the time to peak plasma 3-OMG level (p < 0.0001) after the first meal but there was no difference after the second meal. [Diabetologia (1998) 41: 577±583]

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Section: Discussionmentioning

confidence: 67%

Section: : 577±583]mentioning

confidence: 99%

The effect of single doses of pramlintide on gastric emptying of two meals in men with IDDM

et al. 1998

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“…Amylin is a 37-amino acid polypeptide co-secreted with insulin 11 . In humans, exogenous administration of amylin and the amylin analogue, pramlintide, slows gastric emptying substantially 11 .…”

Section: Introductionmentioning

confidence: 99%

“…In humans, exogenous administration of amylin and the amylin analogue, pramlintide, slows gastric emptying substantially 11 . Furthermore, at least in animal models, amylin appears to be a more potent physiological regulator of gastric emptying than other enterogastrones, including CCK and glucagon-like peptide-1 (GLP-1) 12 .…”

Section: Introductionmentioning

confidence: 99%

Endogenous amylin and glucagon-like peptide-1 concentrations are not associated with gastric emptying in critical illness

Summers

Bartolomeo

Zaknic

et al. 2014

Acta Anaesthesiol Scand

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“…Relative to insulin therapy alone, single-dose pramlintide supplementation represses postprandial glucagon secretion in T1D subjects , Heptulla et al 2005, Chase et al 2009, Hassan & Heptulla 2009). Furthermore, pramlintide administration delays gastric emptying of both solids and liquids in T1D subjects (Kong et al 1997, Vella et al 2002, Woerle et al 2008, Chase et al 2009). In fact, IAPP deficiency may contribute to the accelerated gastric emptying observed in uncomplicated T1D (Vinik et al 2008, Woerle et al 2008.…”

Section: Iapp Replacement In Type 1 Diabetesmentioning

confidence: 99%

IAPP and type 1 diabetes: implications for immunity, metabolism and islet transplants

Denroche

Verchere

2018

Journal of Molecular Endocrinology

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Islet amyloid polypeptide (IAPP), the main component of islet amyloid in type 2 diabetes and islet transplants, is now recognized as a contributor to beta cell dysfunction. Increasingly, evidence warrants its investigation in type 1 diabetes owing to both its immunomodulatory and metabolic actions. Autoreactive T cells to IAPP-derived epitopes have been described in humans, suggesting that IAPP is an islet autoantigen in type 1 diabetes. In addition, although aggregates of IAPP have not been implicated in type 1 diabetes, they are potent pro-inflammatory stimuli to innate immune cells, and thus, could influence autoimmunity. IAPP aggregates also occur rapidly in transplanted islets and likely contribute to islet transplant failure in type 1 diabetes through sterile inflammation. In addition, since type 1 diabetes is a disease of both insulin and IAPP deficiency, clinical trials have examined the potential benefits of IAPP replacement in type 1 diabetes with the injectable IAPP analogue, pramlintide. Pramlintide limits postprandial hyperglycemia by delaying gastric emptying and suppressing hyperglucagonemia, underlining the possible role of IAPP in postprandial glucose metabolism. Here, we review IAPP in the context of type 1 diabetes: from its potential involvement in type 1 diabetes pathogenesis, through its role in glucose metabolism and use of IAPP analogues as therapeutics, to its potential role in clinical islet transplant failure and considerations in this regard for future beta cell replacement strategies.

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Infusion of pramlintide, a human amylin analogue, delays gastric emptying in men with IDDM

Cited by 121 publications

References 25 publications

The effect of single doses of pramlintide on gastric emptying of two meals in men with IDDM

The effect of single doses of pramlintide on gastric emptying of two meals in men with IDDM

Endogenous amylin and glucagon-like peptide-1 concentrations are not associated with gastric emptying in critical illness

IAPP and type 1 diabetes: implications for immunity, metabolism and islet transplants

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