Effect of jejunoileal bypass in the rat on the enteroinsular axis
Abstract
The effect of jejunoileal bypass (JIB) on the enteroinsular axis was studied in vivo and in vitro in the rat. Glucose, insulin and GIP responses to oral glucose were compared in JIB and control rats. The effect of glucose and GIP on insulin release from the isolated perfused pancreas of the same animals was investigated to determine if JIB altered the sensitivity of the β cell. Immunocytochemical studies of gut and pancreas were also carried out.
Glucose, insulin and GIP responses to a glucose load were blunted after JIB, although basal GIP levels were elevated in these animals. The insulin response of the perfused JIB pancreas to GIP was 70% reduced from controls although the insulin response to glucose appeared normal. The size and area of JIB islets were unchanged from controls as was the distribution of insulin, glucagon, somatostatin and pancreatic polypeptide. GIP immunoreactive cells were present in all regions of the intestine including the JIB blind loop. This study confirms the findings of others that a relationship exists between reduced GIP and insulin response to oral glucose after JIB, and indicates that a decrease in sensitivity of the β cell to GIP occurs following JIB that is not rapidly reversible. GIP secreted from blind loop mucosa may contribute to the high basal GIP found in JIB rats and may be causally connected to the fall in β cell sensitivity.
References (12)
- D.L. Sarson et al.
Jejunoileal bypass: A model for the study of the entero-insular axis
Regul. Peptides
(1982) - P.J. Corso et al.
Intestinal bypass in morbid obesity
Surg. Gynecol. Obstet.
(1971) - D.L. Sarson et al.
Radioimmunoassay of gastric inhibitory polypeptide (GIP) and its release in morbid obesity and following jejuno-ileal bypass
J. Endocrinol.
(1979) - D.L. Sarson et al.
Gut hormone changes after jejunoileal (JIB) or biliopancreatic (BPB) bypass surgery for morbid obesity
Internat. J. Obesity
(1981) - G.M. Grodsky et al.
Effect of pulse administration of glucose or glucagon on insulin secretion in vitro
Metabolism
(1967) - A.G.E. Pearse et al.
Bifunctional reagents as vapour and liquid phase fixatives for immunohistochemistry
Histochem. J.
(1975)
Cited by (26)
Improved glucose tolerance in rats treated with the dipeptidyl peptidase IV (CD26) inhibitor ile-thiazolidide
1999, Metabolism: Clinical and ExperimentalThe incretins glucose-dependent insulinotropic polypeptide (GIP1–42) and truncated forms of glucagon-like peptide-1 (GLP-1) are hormones released from the gut in response to ingested nutrients, which act on the pancreas to potentiate glucose-induced insulin secretion. These hormones are rapidly inactivated by the circulating enzyme dipeptidyl peptidase IV ([DPIV] CD26). This study describes the effect on glucose tolerance and insulin secretion of inhibiting endogenous DPIV in the rat using Ile-thiazolidide, a specific DPIV inhibitor. High-performance liquid chromatography (HPLC) analysis of plasma following in vivo administration of 125I-labeled peptides showed that inhibition of DPIV by about 70% prevented the degradation of 90.0% of injected 125I-GLP-17–36 after 5 minutes, while only 13.4% remained unhydrolyzed in rats not treated with the DPIV-inhibiting agent after only 2 minutes. Ile-thiazolidide treatment also increased the circulating half-life of intact GLP-17–36 released in response to intraduodenal (ID) glucose (as measured by N-terminal specific radioimmunoassay [RIA]). In addition, inhibition of DPIV in vivo resulted in an earlier increase and peak of plasma insulin and a more rapid clearance of blood glucose in response to ID glucose challenge. When considered with the HPLC data, these results suggest that the altered insulin profile is an incretin-mediated response. DPIV inhibition resulting in improved glucose tolerance may have therapeutic potential for the management of type 2 diabetes mellitus.
Surgery for obesity
1996, Endocrinology and Metabolism Clinics of North AmericaFor decades, conventional wisdom has considered obesity a disease of bad habits and weak will power. There has been tremendous reluctance to treat with either drugs or surgery a disease believed by many to be within the control of those affected. With new information on the ob gene in mice and the beta-3 receptor mutation in humans, it is becoming clear that obesity is a physiologically controlled variable like high blood pressure.32, 38, 73, 130, 178, 185 With this in mind, it is no surprise that only chronic treatments will provide a lasting solution to the problem of obesity. This explains why short-term behavior modification, diet, exercise, and drugs have been disappointing in their long-term success. Surgery with its inherent permanence clearly has the best long-term success in treating the obese condition.
The history of surgery for the treatment of obesity is long and remarkable. The original attempts to provide surgical treatment occurred in a period of time when it was perceived that bad eating and exercise habits were being treated operatively in patients too weak-willed to follow the safer medical treatments of diet and exercise. Although Kremen and colleagues reported the use of ileal bypass for extreme obesity in one patient in 1954, Payne and co-workers128 were the first to treat a series of patients for obesity with gastrointestinal surgery. Their original operation described in 1963 was the jejunocolic bypass and proved to have serious side effects as well as unacceptable mortality (Fig. 1). The jejunocolic bypass was designed to be reversed after adequate weight had been lost. Restoring the intestinal continuity, however, resulted in regain of the lost weight, and Payne's subsequent work evaluated the potential of jejunoileal bypass as a long-term surgical answer to severe obesity. That work resulted in a procedure which anastamosed 14 inches of jejunum end-to-side to 4 inches of distal ileum. This jejunoileal bypass remained the standard operation for obesity until the advent of gastric procedures.127 Mason and others developed gastric reduction procedures, two of which, the vertically banded gastroplasty and the roux-en-Y gastric bypass, have become the current standard for gastrointestinal obesity surgery.
As surgery for obesity has developed and improved, much has been learned from these procedures about the control of food intake and body weight in humans. This article reviews the development of these surgical approaches with an emphasis on the present state of the surgical treatment as well as the insights that have been gained into the physiologic controls of obesity.
The enteroinsular axis in dipeptidyl peptidase IV-negative rats
1996, Metabolism: Clinical and ExperimentalEvidence has accumulated that the incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1(7–36) amide) are degraded and rendered biologically inactive in plasma by the enzyme dipeptidyl peptidase IV (DPIV). A strain of Fischer rats lacking the DPIV enzyme were used in the current investigation as a model for examining the enteroinsular axis under conditions in which normal inactivation of GIP and GLP-1(7–36) does not occur. This was assessed by comparing GIP and GLP-1(7–36) responses following oral glucose in normal versus DPIV-deficient Fischer rats, and by comparing the insulinotropic potency of both peptides in the perfused pancreas of both groups. The insulin response to an oral glucose challenge was decreased slightly in DPIV-negative rats compared with control animals. Of the two incretins, the GIP response to oral glucose was reduced by 50% compared with controls, whereas GLP-1(7–36) release in response to glucose was unchanged. A decrease of 30% in the sensitivity of the perfused pancreas of DPIV-negative rats to GIP was observed, whereas the insulin response to GLP(7–36) was identical in both groups. Incubation of both peptides in plasma from DPIV-positive and -negative rats was performed to determine the effect of the presence or absence of DPIV on the insulinotropic activity of GLP-1(7–36) and GIP in the isolated perfused rat pancreas. Incubation in plasma from DPIV-positive rats resulted in a 65% decrease in insulinotropic activity of both incretins compared with incubation in plasma from DPIV-deficient rats. It was hypothesized that the reduced GIP response and decreased sensitivity of the pancreas to GIP are compensatory mechanisms that maintain insulin and glucose levels within a normal range despite abnormal degradation of GIP. An explanation of the lack of effect of the absence of DPIV on the GLP-1(7–36) response to oral glucose and insulinotropic action of this peptide must await further study.
Prevention of diabetes by thymic hormone in alloxan-treated rats
1994, European Journal of PharmacologyWe investigated the effects of facteur thymique sérique (FTS), a thymic peptide hormone, on alloxan- and streptozotocin-induced diabetes in rats. Pretreatment with intravenous injection of FTS significantly suppressed both alloxan- and streptozotocin-induced hyperglycemia. The effects of FTS were time dependent. FTS suppressed hyperglycemia in a dose range of 1–6600 μg/kg. Alloxan-induced hyperglycemia was completely prevented when FTS was injected in doses of 40–50 μg/kg 1 min before injection of alloxan. Histological examination of islet areas showed that alloxan-induced destruction of β-cells was inhibited by FTS. FTS had no significant effects on lymphocyte subsets and immunity-related cells or on plasma superoxide dismutase activity and total glutathione level. The blood half-life time of exogenously injected FTS was short (2–3 min), indicating acute internalization of FTS into pancreatic β-cells. Our results suggested that FTS acutely and directly blocks some initial effect of alloxan, preventing the destruction of β-cells.
An overview of gastrointestinal endocrine physiology
1993, Endocrinology and Metabolism Clinics of North AmericaBrain and gut peptides, metabolic actions, receptors, and peptide analogues are reviewed in this article, which concentrates on information that has been derived from recent studies, many of which involve the use of molecular biology techniques.
A rapid, sensitive, and easy-to-perform solid phase insulin radioimmunoassay
1992, Life SciencesAccurate measurement of basal insulin release in perifusion, perfusion and low-density β-cell preparations has been difficult with present assays. A simple competitive, equilibrium, 15-hour insulin assay using 125I-insulin with microtiter immobilized antubody, has been developed. This method, a Solid-phase-RadioImmunoAssay (SPRIA), is very sensitive and has a broad useful range (1 - 64 μU/ml). For a test series of 4 standard curves, interassay variation between controls of 1, 4, 16, and 64 μU/ml was ±5.2% (SEM) and intra-assay variation over the range of standards between 0.5 to 5.1% (SEM). Nonspecific binding was not significantly different from empty borosilicate culture tubes; 4.0 ± 0.4 and 3.5 ± 0.5 counts/minute (mean ± SEM; n = 54), respectively. This SPRIA can be used with existing γ-counters, while reducing the radioactive and glass waste presently produced by RIA (test-tube can be reused). The radioactive of unused test-tubes was compared againts test-tubes used for greater than 10 assays, values were 3.5 ± 0.5 and 4.4 ± 0.6 counts/minute (mean ± SEM; n = 54), respectively. Results of an oral glucose tolerance test (oGTT) performed on four male Wistar Fursth rats showed a close correlation between SPRIA and RIA insulin values (linear regression, r2 = 0.990). This SPRIA measured plasma insulin levels from a human oGTT with a variation of ≤3.7% (SSEM0 between sample triplicates. Standard curves from the three commonly measured insulin isoforms (human, rat and porcine) showed a high correlation (mulitiple linear regression, r2 = 0.998, n = 5 standard curves). In order to determine SPRIA's ability to measure acid extracts, insulin recovery from 2N acetic acid was compared against insulin recovery from Dullbecco's Modified Eagles medium (DME). The insulin recovery from 2N acetic acid was greater than 90% of that achieved with DME. in conclusion, an easy-to-perform assay which is deal for the rapid quantification of insulin from isolated islets of Langerhans, isolated β-cells, acetic acid extracts or plasma with greater sensitivity, and less waste than the conventional RIA has been developed.