RGD Reference Report - Impaired hyperglycemia-induced delay in gastric emptying in patients with type 1 diabetes deficient for islet amyloid polypeptide. - Rat Genome Database

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Impaired hyperglycemia-induced delay in gastric emptying in patients with type 1 diabetes deficient for islet amyloid polypeptide.

Authors: Woerle, HJ  Albrecht, M  Linke, R  Zschau, S  Neumann, C  Nicolaus, M  Gerich, JE  Goke, B  Schirra, J 
Citation: Woerle HJ, etal., Diabetes Care. 2008 Dec;31(12):2325-31.
RGD ID: 2313357
Pubmed: PMID:19033417   (View Abstract at PubMed)
PMCID: PMC2584190   (View Article at PubMed Central)
DOI: DOI:10.2337/dc07-2446   (Journal Full-text)

OBJECTIVE: Slowing of gastric emptying by hyperglycemia, a physiological response to minimize postprandial hyperglycemia, may be impaired in patients with type 1 diabetes. The causes and consequences on glucose homeostasis are unknown. RESEARCH DESIGN AND METHODS: Consequences of euglycemia- and hyperglycemia-induced changes in gastric emptying on postprandial glucose fluxes and excursions were studied in 10 healthy subjects and 15 type 1 diabetic subjects after ingestion of a mixed meal using the double isotope approach ([6,6-(2)H(2)] and [1-(13)C]glucose) and scintigraphic measurements of gastric emptying. RESULTS: Gastric emptying was greater in type 1 diabetic subjects (90-120 min, P < 0.03), and 50% retention times were comparable in healthy subjects and type 1 diabetic subjects (167 +/- 8 vs. 152 +/- 10, P = 0.32). Hyperglycemia markedly delayed gastric emptying in healthy subjects but did not alter it in type 1 diabetic subjects (50% retention time 222 +/- 18 vs. 167 +/- 8 min, P = 0.003 and 148 +/- 9 vs. 152 +/- 10 min, P = 0.51). Plasma islet amyloid polypeptide (IAPP) increased approximately fourfold in healthy subjects (P < 0.001), whereas it was undetectable in type 1 diabetic subjects. IAPP replacement, using the analog pramlintide, in type 1 diabetic subjects slowed gastric emptying to a comparable extent, as did hyperglycemia in healthy subjects (P < 0.14), and greatly reduced postprandial hyperglycemia (P < 00.1). Meal-derived glucose appearance in plasma (10.7 +/- 0.5 vs. 6.8 +/- 0.7 mumol . kg(-1) . min(-1), P < 0.001) was reduced, and splanchnic glucose sequestration increased (14.0 +/- 3.0 vs. 25.0 +/- 6.0%, P = 0.04). CONCLUSIONS: In patients with type 1 diabetes the ability to delay gastric emptying in response to hyperglycemia is impaired. This impairment contributes to exaggerated rates of meal-derived glucose appearance and, ultimately, postprandial glucose excursions.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IAPPHumantype 1 diabetes mellitus  IEP protein:decreased expression:plasmaRGD 
IappRattype 1 diabetes mellitus  ISOIAPP (Homo sapiens)protein:decreased expression:plasmaRGD 
IappMousetype 1 diabetes mellitus  ISOIAPP (Homo sapiens)protein:decreased expression:plasmaRGD 

Objects Annotated

Genes (Rattus norvegicus)
Iapp  (islet amyloid polypeptide)

Genes (Mus musculus)
Iapp  (islet amyloid polypeptide)

Genes (Homo sapiens)
IAPP  (islet amyloid polypeptide)


Additional Information