Duodenal Sodium/Glucose Cotransporter 1 Expression Under Fasting Conditions Is Associated With Postload Hyperglycemia

J Clin Endocrinol Metab. 2017 Nov 1;102(11):3979-3989. doi: 10.1210/jc.2017-00348.

Abstract

Context: Type 2 diabetes (T2DM) is associated with a higher intestinal expression of the glucose transporters sodium/glucose cotransporter 1 (SGLT-1) and glucose transporter 2 (GLUT-2). It is currently unsettled whether prediabetes conditions characterized by postprandial hyperglycemia, such as impaired glucose tolerance (IGT) and normal glucose tolerance (NGT) with 1-hour postload glucose ≥155 mg/dL (8.6 mmol/L) (NGT-1h-high) are associated with increased expression of these glucose carriers in the intestine.

Objective: We evaluated whether duodenal abundance of SGLT-1 and GLUT-2 is augmented in subjects with IGT and NGT-1h-high, in comparison with subjects with NGT and 1-hour postload glucose ˂155 mg/dL (NGT-1h-low).

Design: Cross-sectional.

Patients: A total of 54 individuals underwent an upper gastrointestinal endoscopy.

Main outcome measures: Duodenal SGLT-1 and GLUT-2 protein and messenger RNA levels were assessed by Western blot and reverse transcription polymerase chain reaction, respectively.

Results: Of the 54 subjects examined, 18 had NGT-1h-low, 12 had NGT-1h-high, 12 had IGT, and 12 had T2DM. Duodenal SGLT-1 protein and messenger RNA levels were significantly higher in individuals with NGT-1h-high, IGT, or T2DM in comparison with NGT-1h-low subjects. GLUT-2 abundance was higher in individuals with T2DM in comparison with NGT-1h-low subjects; no substantial increase in GLUT-2 expression was observed in NGT-1h-high or IGT individuals. Univariate correlations showed that duodenal SGLT-1 abundance was positively correlated with 1-hour postload plasma glucose levels (r = 0.44; P = 0.003) but not with fasting or 2-hour postload glucose levels.

Conclusions: Duodenal SGLT-1 expression is increased in individuals with 1-hour postload hyperglycemia or IGT, as well as in subjects with T2DM, and it positively correlates with early postload glucose excursion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism
  • Duodenum / metabolism*
  • Fasting / metabolism*
  • Female
  • Glucose Intolerance / complications
  • Glucose Intolerance / genetics
  • Glucose Intolerance / metabolism
  • Glucose Tolerance Test
  • Glucose Transporter Type 2 / genetics
  • Glucose Transporter Type 2 / metabolism
  • Humans
  • Hyperglycemia / complications
  • Hyperglycemia / genetics*
  • Hyperglycemia / metabolism
  • Male
  • Middle Aged
  • Postprandial Period
  • Prediabetic State / complications
  • Prediabetic State / genetics
  • Prediabetic State / metabolism
  • Sodium-Glucose Transporter 1 / genetics*
  • Sodium-Glucose Transporter 1 / metabolism

Substances

  • Glucose Transporter Type 2
  • SLC2A2 protein, human
  • SLC5A1 protein, human
  • Sodium-Glucose Transporter 1