Diabetes induced by a high fructose diet

Administration of a sucrose-rich diet (SRD) to normal hamsters induces an insulin-resistant state and a significant increase of insulin secretion and -cell mass. Islets isolated from these animals had a marked increase in glucose metabolism and glucose-induced insulin secretion, at both low and high glucose concentrations. They also presented increased hexokinase (HK) activity, without measurable changes in glucokinase (GK) activity. In this study we measured HK and GK activity in homogenates of islets isolated from normal control and SRD-fed hamsters, as well as in their particulate and cytosolic fractions. We also measured transcription rate (mRNA by reverse transcriptase PCR) and expression levels (Western blotting) of both enzymes in these islets. We found an increase in HK activity and expression levels, without measurable changes in HK mRNA level in SRD-fed animals. Whereas a similar GK activity was measured in homogenates of islets isolated from both groups, such activity was significantly higher in the cytosolic fraction of SRD islets. On the other hand, GK transcription rate and expression level were similar in both experimental groups. Our results suggest that the increased -cell secretory response to low glucose can be partly ascribed to an increased activity of islet HK consecutive to an enhanced expression of the enzyme, while the enhanced response to high glucose could be due to changes in GK compartmentalization.

Section: Introductionmentioning

confidence: 99%

Enhanced expression of hexokinase I in pancreatic islets induced by sucrose administration

Maiztegui

Borelli²,

Massa³

et al. 2006

“…The chronic administration of a sucrose-rich diet (SRD) to normal rats induces an insulin-resistant state characterized by moderate fasting hyperglycemia, increased triglyceride and free fatty acid (FFA) levels, normoinsulinemia and a modest increase in body weight (Cohen et al 1977, Lombardo et al 1996. Islets isolated from these rats have a normal insulin content (Lombardo et al 1996, Del Zotto et al 2002, but their secretion pattern is characterized by the absence of the first peak and the enhancement of the second phase of insulin release in response to glucose , Pighin et al 2003.…”

Section: Introductionmentioning

confidence: 99%

Islet neogenesis: an apparent key component of long-term pancreas adaptation to increased insulin demand

Zotto

Borelli²,

Flores³

et al. 2004

This study aimed to determine the relative importance of different functional and morphological pancreatic changes induced by the chronic administration of a sucrose-rich diet (SRD) to maintain normal glucose homeostasis. Male Wistar rats were fed either sucrose (SRD) or starch (CD) for 6 and 12 months. At both periods, serum glucose and triacylglycerol levels were significantly higher (P<0·05; paired and unpaired Student's t-test) in SRD rats. Serum insulin levels were significantly lower in SRD only at 12 months. At 6 months, the insulin secretion doseresponse curve in SRD rats showed a shift to the left that was no longer observed at 12 months, when SRD islets decreased their response to 16 mM glucose. At 6 months, SRD rats showed a significant increase in -cell volume density (Vvi) and islet cell replication rate, together with a decrease in -cell apoptotic rate. Changes were not detected in the percentage of PDX-1-and islet neogenesis associated protein (INGAP)-positive cells. Conversely, at 12 months, there was a significant decrease in -cell Vvi and in the percentage of PDX-1-positive cells; the islet cell replication rate was not modified, and the number of apoptotic -cells increased significantly. No signs of increased neogenesis or INGAP-positive cells were recorded at any period in SRD rats. Our results show that SRD rats are unable to develop functional and morphological pancreatic reactive changes sufficient to maintain normal glucose and triacylglycerol levels for a long period. Such failure could be ascribed to their inability to increase the rate of neogenesis and of INGAP production.

“…Prolonged administration of either a high fructose or sucrose diet to genetically selected rats induces a metabolic syndrome characterised by insulin resistance and decreased glucose tolerance, as well as increased plasma triglyceride and cholesterol levels (Cohen et al 1977, Cohen 1978. We have previously reported that administration of a sucrose-rich diet (SRD) to normal rats for 6 months induced such metabolic abnormalities, together with a significant increase in both pancreatic islet number and -cell area (Lombardo et al 1996).…”

Section: Introductionmentioning

confidence: 99%

Mechanisms involved in the beta-cell mass increase induced by chronic sucrose feeding to normal rats

Zotto¹,

Dumm²,

Drago³

et al. 2002

The aim of the present study was to clarify the mechanisms by which a sucrose-rich diet (SRD) produces an increase in the pancreatic -cell mass in the rat. Normal Wistar rats were fed for 30 weeks either an SRD (SRD rats; 63% wt/wt), or the same diet but with starch instead of sucrose in the same proportion (CD rats). We studied body weight, serum glucose and triacylglycerol levels, endocrine tissue and -cell mass, -cell replication rate (proliferating cell nuclear antigen; PCNA), islet neogenesis (cytokeratin immunostaining) and -cell apoptosis (propidium iodide). Body weight (g) recorded in the SRD rats was significantly (P<0·05) larger than that of the CD group (556·0 8·3 vs 470·0 13·1). Both serum glucose and triacylglycerol levels (mmol/l) were also significantly higher (P<0·05) in SRD than in CD rats (serum glucose, 8·11 0·14 vs 6·62 0·17; triacylglycerol, 1·57 0·18 vs 0·47 0·04). The number of pancreatic islets per unit area increased significantly (P<0·05) in SRD rats (3·29 0·1 vs 2·01 0·2). A significant increment (2·6 times) in the mass of endocrine tissue was detected in SRD animals, mainly due to an increase in the -cell mass (P=0·0025). The islet cell replication rate, measured as the percentage of PCNA-labelled cells increased 6·8 times in SRD rats (P<0·03). The number of apoptotic cells in the endocrine pancreas decreased significantly (three times) in the SRD animals (P=0·03). The cytokeratin-positive area did not show significant differences between CD and SRD rats. The increase of -cell mass induced by SRD was accomplished by an enhanced replication of cells together with a decrease in the rate of -cell apoptosis, without any evident participation of islet neogenesis. This pancreatic reaction was unable to maintain serum glucose levels of these rats at the level measured in CD animals.