Enteroendocrine K and L cells in healthy and type 2 diabetic individuals

TY - JOUR

T1 - Enteroendocrine K and L cells in healthy and type 2 diabetic individuals

AU - Jorsal, Tina

AU - Rhee, Nicolai A.

AU - Pedersen, Jens

AU - Wahlgren, Camilla D.

AU - Mortensen, Brynjulf

AU - Jepsen, Sara L.

AU - Jelsing, Jacob

AU - Dalbøge, Louise S.

AU - Vilmann, Peter

AU - Hassan, Hazem

AU - Hendel, Jakob W.

AU - Poulsen, Steen S.

AU - Holst, Jens J.

AU - Vilsbøll, Tina

AU - Knop, Filip K.

PY - 2018/2/1

Y1 - 2018/2/1

N2 - Aims/hypothesis: Enteroendocrine K and L cells are pivotal in regulating appetite and glucose homeostasis. Knowledge of their distribution in humans is sparse and it is unknown whether alterations occur in type 2 diabetes. We aimed to evaluate the distribution of enteroendocrine K and L cells and relevant prohormone-processing enzymes (using immunohistochemical staining), and to evaluate the mRNA expression of the corresponding genes along the entire intestinal tract in individuals with type 2 diabetes and healthy participants. Methods: In this cross-sectional study, 12 individuals with type 2 diabetes and 12 age- and BMI-matched healthy individuals underwent upper and lower double-balloon enteroscopy with mucosal biopsy retrieval from approximately every 30 cm of the small intestine and from seven specific anatomical locations in the large intestine. Results: Significantly different densities for cells positive for chromogranin A (CgA), glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, peptide YY, prohormone convertase (PC) 1/3 and PC2 were observed along the intestinal tract. The expression of CHGA did not vary along the intestinal tract, but the mRNA expression of GCG, GIP, PYY, PCSK1 and PCSK2 differed along the intestinal tract. Lower counts of CgA-positive and PC1/3-positive cells, respectively, were observed in the small intestine of individuals with type 2 diabetes compared with healthy participants. In individuals with type 2 diabetes compared with healthy participants, the expression of GCG and PYY was greater in the colon, while the expression of GIP and PCSK1 was greater in the small intestine and colon, and the expression of PCSK2 was greater in the small intestine. Conclusions/interpretation: Our findings provide a detailed description of the distribution of enteroendocrine K and L cells and the expression of their products in the human intestinal tract and demonstrate significant differences between individuals with type 2 diabetes and healthy participants. Trial registration:: NCT03044860.

AB - Aims/hypothesis: Enteroendocrine K and L cells are pivotal in regulating appetite and glucose homeostasis. Knowledge of their distribution in humans is sparse and it is unknown whether alterations occur in type 2 diabetes. We aimed to evaluate the distribution of enteroendocrine K and L cells and relevant prohormone-processing enzymes (using immunohistochemical staining), and to evaluate the mRNA expression of the corresponding genes along the entire intestinal tract in individuals with type 2 diabetes and healthy participants. Methods: In this cross-sectional study, 12 individuals with type 2 diabetes and 12 age- and BMI-matched healthy individuals underwent upper and lower double-balloon enteroscopy with mucosal biopsy retrieval from approximately every 30 cm of the small intestine and from seven specific anatomical locations in the large intestine. Results: Significantly different densities for cells positive for chromogranin A (CgA), glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, peptide YY, prohormone convertase (PC) 1/3 and PC2 were observed along the intestinal tract. The expression of CHGA did not vary along the intestinal tract, but the mRNA expression of GCG, GIP, PYY, PCSK1 and PCSK2 differed along the intestinal tract. Lower counts of CgA-positive and PC1/3-positive cells, respectively, were observed in the small intestine of individuals with type 2 diabetes compared with healthy participants. In individuals with type 2 diabetes compared with healthy participants, the expression of GCG and PYY was greater in the colon, while the expression of GIP and PCSK1 was greater in the small intestine and colon, and the expression of PCSK2 was greater in the small intestine. Conclusions/interpretation: Our findings provide a detailed description of the distribution of enteroendocrine K and L cells and the expression of their products in the human intestinal tract and demonstrate significant differences between individuals with type 2 diabetes and healthy participants. Trial registration:: NCT03044860.

KW - Chromogranin A

KW - Double-balloon enteroscopy

KW - Enteroendocrine cells

KW - Glucagon-like peptide-1

KW - Glucose-dependent insulinotropic polypeptide

KW - Immunohistochemistry

KW - mRNA expression

KW - Peptide YY

KW - Prohormone convertase

KW - Type 2 diabetes

UR - http://www.scopus.com/inward/record.url?scp=85030116080&partnerID=8YFLogxK

U2 - 10.1007/s00125-017-4450-9

DO - 10.1007/s00125-017-4450-9

M3 - Journal article

C2 - 28956082

AN - SCOPUS:85030116080

SN - 0012-186X

VL - 61

SP - 284

EP - 294

JO - Diabetologia

JF - Diabetologia

IS - 2

ER -