High-fat feeding stimulates endocrine, glucose-dependent insulinotropic polypeptide (GIP)-expressing cell hyperplasia in the duodenum of Wistar rats.
OBJECTIVE
Incretins are hormones released by enteroendocrine cells in response to meals, depending upon absorption of nutrients. The present study aimed to elucidate the mechanisms through which a high-fat diet (HFD) induces insulin resistance and insulin hypersecretion by focusing on the effects on enteroendocrine cells, especially those secreting glucose-dependent insulinotropic polypeptide (GIP).


METHODS
Forty male Wistar rats, 4 months old, were randomised into two groups; one group received a chow diet and the other one received a purified tripalmitin-based HFD ad libitum. An OGTT was performed every 10 days and histological and immunofluorescence evaluations of the duodenum were obtained at 60 days from the beginning of the diets. Plasma glucose, insulin, GIP and glucagon-like peptide-1 (GLP-1) levels were measured. Immunofluorescence analysis of duodenal sections for pancreatic duodenal homeobox-1 (PDX-1), KI67, GLP-1, GIP and insulin were performed.


RESULTS
Compared with chow diet, HFD induced a progressive significant increase of the glucose, insulin and GIP responses to OGTT, whereas GLP-1 circulating levels were reduced over time. After 60 days of HFD, cellular agglomerates of KI67 and PDX-1 positive cells, negative for insulin and GLP-1 but positive for GIP staining, were found inside the duodenal mucosa, and apoptosis was significantly increased.


CONCLUSIONS
With the limitation that we could not establish a causal relationship between events, our study shows that HFD stimulates duodenal proliferation of endocrine cells differentiating towards K cells and oversecreting GIP. The progressive increment of GIP levels might represent the stimulus for insulin hypersecretion and insulin resistance.
Gniuli
D
D
Department of Internal Medicine and Diabetes Unit, Università Cattolica del Sacro Cuore, L.go Gemelli 8, 00168 Roma, Italy.
Calcagno
A
A
Dalla Libera
L
L
Calvani
R
R
Leccesi
L
L
Caristo
M E
ME
Vettor
R
R
Castagneto
M
M
Ghirlanda
G
G
Mingrone
G
G
D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D004041:Dietary Fats / Q000378:metabolism*; D004386:Duodenum / Q000378:metabolism* / Q000473:pathology*; D019858:Enteroendocrine Cells / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D005951:Glucose Tolerance Test; D006965:Hyperplasia / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D007328:Insulin / Q000097:blood; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1