Beta-cell sensitivity to insulinotropic gut hormones is reduced after gastric bypass surgery

Gut ◽  
2019 ◽  
Vol 68 (10) ◽  
pp. 1838-1845 ◽  
Author(s):  
Marzieh Salehi ◽  
Amalia Gastaldelli ◽  
David A D’Alessio
Keyword(s):  
Gastric Bypass ◽  
Insulin Secretion ◽  
Gastric Bypass Surgery ◽  
Gut Hormones ◽  
Normal Glucose Tolerance ◽  
Cell Sensitivity ◽  
Glucose Levels ◽  
Normal Glucose ◽  
Glucagon Like Peptide 1 ◽  
Glucose Stimulated Insulin Secretion

ObjectivePostprandial hyperinsulinaemia after Roux-en Y gastric bypass (GB) has been attributed to rapid nutrient flux from the gut, and an enhanced incretin effect. However, it is unclear whether surgery changes islet cell responsiveness to regulatory factors. This study tested the hypothesis that β-cell sensitivity to glucagon like-peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) is attenuated after GB.DesignTen non-diabetic subjects with GB, and 9 body mass index (BMI)-matched and age-matched non-surgical controls (CN) with normal glucose tolerance had blood glucose clamped at ~7.8 mM on three separate days. Stepwise incremental infusions of GLP-1 (15, 30, 60, 120 and 300 ng/LBkg/h), GIP (75, 150, 300, 600 and 1200 ng/LBkg/h) or saline were administered from 90 to 240 min and insulin secretion measured.ResultsGB subjects had similar fasting glucose levels but lower fasting insulin compared with CN, likely due to increased insulin clearance. The average insulin secretion rates (ISRs) to 7.8 mM glucose were ~30% lower in GB relative to CN subjects. However, incretin-stimulated ISRs, adjusted for insulin sensitivity and glucose-stimulated insulin secretion, were even more attenuated in the GB subjects, by threefold to fourfold (AUCISR(90−240 min) during GLP-1 and GIP: 47±8 and 44±12 nmol in GB and 116±16 and 161±44 in CN; p<0.01).ConclusionAfter GB, the sensitivity of insulin secretion to both glucose and incretins is diminished.

scholarly journals Mechanisms of action of a carbohydrate-reduced, high-protein diet in reducing the risk of postprandial hypoglycemia after Roux-en-Y gastric bypass surgery

2019 ◽  
Vol 110 (2) ◽  
pp. 296-304 ◽  
Author(s):  
Daniel Kandel ◽  
Kirstine Nyvold Bojsen-Møller ◽  
Maria Saur Svane ◽  
Amirsalar Samkani ◽  
Arne Astrup ◽  
...  
Keyword(s):  
Gastric Bypass ◽  
Insulin Secretion ◽  
Cell Function ◽  
Gastric Bypass Surgery ◽  
High Protein Diet ◽  
Glucagon Secretion ◽  
Glucose Variability ◽  
High Protein ◽  
Β Cell Function ◽  
Glucagon Like Peptide 1

ABSTRACT Background Postprandial hypoglycemia is a risk after Roux-en-Y gastric bypass (RYGB). Objectives We speculated that a carbohydrate-reduced, high-protein (CRHP) diet might reduce the risk of hypoglycemia and therefore compared the acute effects of a conventionally recommended (CR) diet and CRHP diet [55/30 energy percent (E%) carbohydrate and 15/30 E% protein, respectively] in RYGB patients. Methods Ten individuals (2 males, 8 females, mean ± SD age 47 ± 7 y; stable body mass index 31 ± 6 kg/m2; 6 ± 3 y post-RYGB) with recurrent postprandial hypoglycemia documented by plasma glucose (PG) ≤3.4 mmol/L were examined on 2 d with isoenergetic CRHP or CR diets comprising a breakfast and subsequent lunch meal. Results Peak PG was significantly reduced on the CRHP diet after breakfast and lunch by 11% and 31% compared with the CR diet. Nadir PG increased significantly on CRHP (by 13% and 9%). Insulin secretion was reduced, and glucagon secretion increased on the CRHP diet after both meals. Glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide secretion were lower after lunch but unaltered after breakfast on CRHP; β-cell function and insulin clearance were unchanged. Conclusions The CRHP diet lowered glucose excursions and reduced insulin secretion and incretin hormone responses, but enhanced glucagon responses compared with the CR diet. Taken together, the results may explain the decreased glucose variability and lower risk of postprandial hypoglycemia. This study was registered at clinicaltrials.gov as NCT02665715.

Effects of somatostatin-28 on circulating concentrations of insulin and gut hormones in sheep

1996 ◽  
Vol 151 (1) ◽  
pp. 107-112 ◽  
Author(s):  
P A Martin ◽  
A Faulkner
Keyword(s):  
Insulin Secretion ◽  
Basal Insulin ◽  
Gut Hormones ◽  
Serum Concentrations ◽  
Nutrient Partitioning ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Glucose Stimulated Insulin Secretion

Abstract The effects of intravenous somatostatin-28 (S28) infusion on glucose-stimulated and glucagon-like peptide-1(7–36)amide (GLP-1)-augmented insulin secretion were studied in sheep. S28 was infused via a jugular catheter for 15 min at a rate of 1·1 pmol/kg/min either alone or together with GLP-1 and/or glucose. S28 infusion did not significantly lower circulating basal insulin concentrations in fed sheep. Glucose-stimulated insulin secretion was significantly inhibited by S28 infusion, serum concentrations decreasing from about 200 to 150 pmol/l. GLP-1 significantly augmented glucose-stimulated insulin secretion, serum concentrations increasing from about 230 to 280 pmol/l. S28 completely counteracted this effect of GLP-1. S28 infusion also significantly decreased the circulating concentrations of glucose-dependent insulinotrophic polypeptide (GIP) and GLP-1 in fed sheep (from about 110 to 45 pmol/l for GIP and from about 25 to 15 pmol/l for GLP-1). The physiological implications of these observations are discussed with particular reference to the ruminant. It is concluded that S28 may have an important endocrine role in the control of insulin secretion and regulation of nutrient partitioning. Journal of Endocrinology (1996) 151, 107–112

scholarly journals The role of incretins on insulin function and glucose homeostasis

Endocrinology ◽  
2021 ◽  
Author(s):  
Jens Juul Holst ◽  
Lærke Smidt Gasbjerg ◽  
Mette Marie Rosenkilde
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Postprandial Glucose ◽  
Normal Glucose Tolerance ◽  
Incretin Effect ◽  
Normal Glucose ◽  
Individual Contributions ◽  
Glucagon Like Peptide 1 ◽  
The Individual

Abstract The incretin effect – the amplification of insulin secretion after oral versus intravenous administration of glucose as a mean to improve glucose tolerance – was suspected even before insulin was discovered, and today we know that the effect is due to the secretion of two insulinotropic peptides, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). But how important is it? Physiological experiments have shown that, because of the incretin effect, we can ingest increasing amounts of amounts of glucose (carbohydrates) without increasing postprandial glucose excursions, which otherwise might have severe consequences. The mechanism behind this is incretin-stimulated insulin secretion. The availability of antagonists for GLP-1 and most recently also for GIP has made it possible to directly estimate the individual contributions to postprandial insulin secretion of a) glucose itself: 26%; b) GIP: 45%; and c) GLP-1: 29%. Thus, in healthy individuals, GIP is the champion. When the action of both incretins is prevented, glucose tolerance is pathologically impaired. Thus, after 100 years of research, we now know that insulinotropic hormones from the gut are indispensable for normal glucose tolerance. The loss of the incretin effect in type 2 diabetes, therefore, contributes greatly to the impaired postprandial glucose control.

STUDIES IN CONGENITAL GENERALIZED LIPODYSTROPHY (SEIP-BERARDINELLI SYNDROME)

1973 ◽  
Vol 72 (3) ◽  
pp. 475-494 ◽  
Author(s):  
Svein Oseid
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Normal Glucose Tolerance ◽  
Juvenile Form ◽  
Congenital Generalized Lipodystrophy ◽  
Glucose Levels ◽  
Normal Glucose ◽  
Glucose Tolerance Tests ◽  
The One ◽  
Adipose Organ

ABSTRACT Six cases of congenital generalized lipodystrophy have been studied at different ages from infancy to adolescence with regard to glucose tolerance, insulin secretion, and insulin sensitivity. During the first few years of life there is normal glucose tolerance. The fasting immuno-reactive insulin (IRI) levels are either slightly elevated or normal. The IRI response to glucose is exaggerated and prolonged, at least from the third year of life. Some degree of insulin resistance is already present in infancy. From the age of 8–10 years glucose tolerance decreases rapidly. The fasting IRI levels are usually grossly elevated, while fasting plasma glucose levels are only moderately elevated or normal. The IRI responses to oral and iv administered glucose, and to tolbutamide are exaggerated; the insulinogenic indices are high. Cortisone primed glucose tolerance tests become abnormal. Insulin resistance is marked, and increases with age. After cessation of growth at approximately 12 years of age, frank diabetes with fasting hyperglycaemia and diabetic glucose tolerance curves developed in the one patient followed beyond this age. Her fasting IRI was increased, but there was a poor IRI response to glucose stimulation, suggesting a partial exhaustion of the β-cells. Her initial IRI response to tolbutamide was still good, but not as brisk as in the younger patients. This type of diabetes is quite different from the juvenile form, and also from the diabetes of older age. It may be causally related to the lack of an adequate adipose organ necessary for the disposal of excesses of glucose, or possibly related to another anti-insulin mechanism.

Sign in / Sign up

Export Citation Format

Share Document