Glucose-dependent Insulinotropic Polypeptide (GIP) Resistance and β-cell Dysfunction Contribute to Hyperglycaemia in Acromegaly

Autor: Pinaki Dutta, Kim Vaiphei, Kanchan K Mukherjee, Sunder Mudaliar, Anil Bhansali, Anura V Kurpad, Vikram Singh Shekhawat, Saroj K. Sinha, Naresh Sachdeva, Shobhit Bhansali, Rakesh Kochhar, Kishor Bhat
Rok vydání: 2019
Předmět:
Adult
Blood Glucose
Male
0301 basic medicine
endocrine system
medicine.medical_specialty
lcsh:Medicine
Gastric Inhibitory Polypeptide
Incretins
Glucagon
Article
Receptors
Gastrointestinal Hormone
03 medical and health sciences
0302 clinical medicine
Insulin resistance
Glucagon-Like Peptide 1
Insulin-Secreting Cells
Internal medicine
Diabetes mellitus
Acromegaly
medicine
Humans
Insulin
Prospective Studies
lcsh:Science
Multidisciplinary
business.industry
lcsh:R
digestive
oral
and skin physiology
medicine.disease
030104 developmental biology
medicine.anatomical_structure
Endocrinology
Diabetes Mellitus
Type 2
Case-Control Studies
Hyperglycemia
Glucose Clamp Technique
Duodenum
Immunohistochemistry
lcsh:Q
Female
Insulin Resistance
business
hormones
hormone substitutes
and hormone antagonists
030217 neurology & neurosurgery
Homeostasis
Hyperglucagonemia
Zdroj: Scientific Reports
Scientific Reports, Vol 9, Iss 1, Pp 1-11 (2019)
ISSN: 2045-2322
DOI: 10.1038/s41598-019-41887-7
Popis: Impaired insulin sensitivity (IS) and β-cell dysfunction result in hyperglycaemia in patients of acromegaly. However, alterations in incretins and their impact on glucose-insulin homeostasis in these patients still remain elusive. Twenty patients of active acromegaly (10 each, with and without diabetes) underwent hyperinsulinemic euglycaemic clamp and mixed meal test, before and after surgery, to measure indices of IS, β-cell function, GIP, GLP-1 and glucagon response. Immunohistochemistry (IHC) for GIP and GLP-1 was also done on intestinal biopsies of all acromegalics and healthy controls. Patients of acromegaly, irrespective of presence or absence of hyperglycaemia, had similar degree of insulin resistance, however patients with diabetes exhibited hyperglucagonemia, and compromised β-cell function despite significantly higher GIP levels. After surgery, indices of IS improved, GIP and glucagon levels decreased significantly in both the groups, while there was no significant change in indices of β-cell function in those with hyperglycaemia. IHC positivity for GIP, but not GLP-1, staining cells in duodenum and colon was significantly lower in acromegalics with diabetes as compared to healthy controls possibly because of high K-cell turnover. Chronic GH excess induces an equipoise insulin resistance in patients of acromegaly irrespective of their glycaemic status. Dysglycaemia in these patients is an outcome of β-cell dysfunction consequent to GIP resistance and hyperglucagonemia.
Databáze: OpenAIRE
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