Abnormal Lipid Accumulation Within the Small Intestinal Mucosa of Children With Juvenile-Onset Diabetes Mellitus

Bobo, Robert C.

doi:10.1001/archpedi.1977.02120220028003

Cited by 6 publications

(2 citation statements)

References 45 publications

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“…Since palmitate is the most abundant saturated FFA [56,57,58] that mainly increases during diabetes, both in humans and in experimental animal models [59], in this study we used it to mimic diabetic hyperlipidemia and insulin resistance in an in vitro model of intestinal L-cells. Our data are in agreement with previous reports that explored intestinal lipid accumulation in several metabolic disorders such as obesity and diabetes [60,61,62].…”

Section: Discussionsupporting

confidence: 94%

Chronic Exposure to Palmitate Impairs Insulin Signaling in an Intestinal L-cell Line: A Possible Shift from GLP-1 to Glucagon Production

Filippello

Urbano

Mauro

et al. 2018

IJMS

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Obesity and type 2 diabetes mellitus (T2DM) are characterized by insulin resistance and impaired glucagon-like peptide-1 (GLP-1) secretion/function. Lipotoxicity, a chronic elevation of free fatty acids in the blood, could affect insulin-signaling in many peripheral tissues. To date, the effects of lipotoxicity on the insulin receptor and insulin resistance in the intestinal L-cells need to be elucidated. Moreover, recent observations indicate that L-cells may be able to process not only GLP-1 but also glucagon from proglucagon. The aim of this study was to investigate the effects of chronic palmitate exposure on insulin pathways, GLP-1 secretion and glucagon synthesis in the GLUTag L-cell line. Cells were cultured in the presence/absence of palmitate (0.5 mM) for 24 h to mimic lipotoxicity. Palmitate treatment affected insulin-stimulated GLP-1 secretion, insulin receptor phosphorylation and IRS-1-AKT pathway signaling. In our model lipotoxicity induced extracellular signal-regulated kinase (ERK 44/42) activation both in insulin stimulated and basal conditions and also up-regulated paired box 6 (PAX6) and proglucagon expression (Gcg). Interestingly, palmitate treatment caused an increased glucagon secretion through the up-regulation of prohormone convertase 2. These results indicate that a state of insulin resistance could be responsible for secretory alterations in L-cells through the impairment of insulin-signaling pathways. Our data support the hypothesis that lipotoxicity might contribute to L-cell deregulation.

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Section: Discussionsupporting

confidence: 94%

Chronic Exposure to Palmitate Impairs Insulin Signaling in an Intestinal L-cell Line: A Possible Shift from GLP-1 to Glucagon Production

Filippello

Urbano

Mauro

et al. 2018

IJMS

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“…Other hormones may also play a role, particularly insulin, which has been reported to produce effects in the small intestine. For example, it has been reported that adolescents with diabetes mellitus exhibit lipid accumulation within proximal jejunum mucosa (Bobo et al, 1977). Insulin has also been shown to decrease chylomicron production in human jejunal explants (Loirdighi et al, 1992), and rodent studies show many effects of insulin resistance on insulin signaling in enterocytes, including increased de novo lipogenesis and altered GLUT2 translocation (Haidari et al, 2002; Tobin et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Intestinal Mucosal Triacylglycerol Accumulation Secondary to Decreased Lipid Secretion in Obese and High Fat Fed Mice

Douglass¹,

Malik²,

Chon³

et al. 2012

Front. Physio.

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The ectopic deposition of fat in liver and muscle during obesity is well established, however surprisingly little is known about the intestine. We used the ob/ob mouse and C57BL6/J mice fed a high fat (HF) diet to examine the effects of obesity and the effects of HF feeding, respectively, on intestinal mucosal triacylglycerol (TG) accumulation. Male C57BL6/J (wild-type, WT) mice were fed low fat (LF; 10% kcal as fat) or HF (45%) diets, and ob/ob mice were fed the LF diet, for 3 weeks. In this time frame, the WT–HF mice did not become obese, enabling independent examination of effects of the HF diet and effects of obesity. Analysis of intestinal lipid extracts from fed and fasted animals demonstrated that the mucosa, like other tissues, accumulates excess lipid. In the fed state, mucosal triacylglycerol (TG) levels were threefold and fivefold higher in the WT–HF and ob/ob mice, respectively, relative to the WT–LF mice. In the fasted state, mucosa from ob/ob mice had threefold higher TG levels relative to WT–LF mucosa. q-PCR analysis of mucosal mRNA from fed state mice showed alterations in the expression of several genes related to both anabolic and catabolic lipid metabolism pathways in WT–HF and ob/ob mice relative to WT–LF controls. Fewer changes were found in mucosal samples from the fasted state animals. Remarkably, oral fat tolerance tests showed a striking reduction in the plasma appearance of an oral fat load in the ob/ob and WT–HF mice compared to WT–LF. Overall, the results demonstrate that the intestinal mucosa accumulates excess TG during obesity. Changes in the expression of lipid metabolic and transport genes, as well as reduced secretion of dietary lipid from the mucosal cells into the circulation, may contribute to the TG accumulation in intestinal mucosa during obesity. Moreover, even in the absence of frank obesity, HF feeding leads to a large decrease in the rate of intestinal lipid secretion.

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Biochemischer und mikromorphologischer Nachweis von Lipiden in der Dünndarmschleimhaut von Patienten mit Diabetes mellitus

et al. 1981

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Hyperlipemia is a frequent finding in diabetes mellitus. As not only the liver, but intestinal mucosa as well synthesizes endogenous lipoproteins, we have investigated the small intestinal mucosal lipid content in 11 adult patients with juvenile onset diabetes and in 7 patients with maturity onset diabetes. Eleven non-diabetic patients served as controls. After a fasting period of 12-14 h blood was drawn for determination of glucose, lipids and glycosylated hemoglobin AI. Then several small bowel biopsies were performed by an hydraulic multiple biopsy tube or endoscopically and the specimens were processed immediately for further biochemical, histochemical and electronmicroscopical workup. Patients with juvenile and with maturity onset diabetes did not differ from controls with regard to serum lipids and to intestinal mucosal lipids determined biochemically. Surprisingly, patients with maturity onset diabetes exhibited a significantly (p less than 0,005) higher concentration of intestinal mucosal triglycerides than patients with juvenile onset diabetes. Fasting blood glucose and hemoglobin AI levels were slightly elevated in both groups of diabetic patients. Histochemically lipid particles were demonstrable in intestinal mucosa of diabetics and of controls with equal variability. The electronmicroscopical appearance of intestinal mucosa did not differ between diabetic patients and controls. Only in one patient with juvenile onset diabetes an accumulation of lipid particles within the cisternae of the Golgi apparatus was observed. In conclusion, neither biochemically, nor histochemically, nor electronmicroscopically an abnormal accumulation of lipids could be found in the small intestinal mucosa of patients with well controlled diabetes mellitus.

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Abnormal Lipid Accumulation Within the Small Intestinal Mucosa of Children With Juvenile-Onset Diabetes Mellitus

Cited by 6 publications

References 45 publications

Chronic Exposure to Palmitate Impairs Insulin Signaling in an Intestinal L-cell Line: A Possible Shift from GLP-1 to Glucagon Production

Chronic Exposure to Palmitate Impairs Insulin Signaling in an Intestinal L-cell Line: A Possible Shift from GLP-1 to Glucagon Production

Intestinal Mucosal Triacylglycerol Accumulation Secondary to Decreased Lipid Secretion in Obese and High Fat Fed Mice

Biochemischer und mikromorphologischer Nachweis von Lipiden in der Dünndarmschleimhaut von Patienten mit Diabetes mellitus

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