Pancreatic Duct Occlusion in the Rat – Short-Term Effects on Oral Glucose Tolerance and Short- and Long-Term Effects on Hormone Content of the Pancreas

Abstract

In a short-term (14 days) and a long-term (84 days) experiment after pancreatic duct occlusion in the rat, we measured the insulin, glucagon and somatostatin content of the pancreas; in the short-term experiment, in addition, we performed an oral glucose tolerance test on the 14th day. Exocrine pancreatic function in the short-term study was monitored on the 9th day – in the long-term study on the 21 st day. In the long-term study, the pancreatic organ was also examined histologically. Occlusion of the pancreatic duct considerably reduces exocrine function. This accords with the histologically observed atrophy of the exocrine parenchyma, above all in the body and tail (after 84 days). 14 days after occlusion, basal plasma glucose and insulin was about the same as in the sham-operated rats. Incremental insulin after the glucose load in occluded rats was delayed for about 30 min, but the pattern of plasma glucose was only insignificantly altered as compared with the sham-operated controls. The insulin content of the pancreas on days 14 and 84 after occlusion was increased, glucagon and somatostatin unchanged. We conclude, that (a) intraductal occlusion of the pancreas is a suitable tool for inducing an atrophy of the exocrine pancreas; (b) in the short-term, after the duct occlusion, oral glucose tolerance is preserved, but the passage of insulin into the blood is delayed and is associated with a high level of insulin in the pancreas; the cause or causes of this coincidence is/are unknown.

Influence of Pancreatic Duct Occlusion on Islet Hormones in Peripheral and Portal Plasma and in the Pancreas of the Mini-Pig

“…Unfortunately, this technique had not been available to us. The smaller increase in body weight in Occ animals is in agree ment with our long-term observations in the rat [20], Whether the two observations are an expression of a lack of digestive enzymes in spite of enzyme substitution is uncertain. In another long-term study in beagles (to date 36 months observation time in this breed) in this laboratory, using a similar enzyme sub stitution, body weight is not changed by oc clusion [Schwüle et al, unpubl.…”

“…Another important pointer suggestive of species differences with respect to the re sponse to occlusion might be the different pancreatic hormone content after occlusion seen in the present study in mini-pigs (de creased somatostatin, stable insulin) and in our earlier study in the rat (stable somatosta tin, increased insulin) [20], Irrespective of any possible interaction between insulin and somatostatin at the islet level, it should be said that in the pig the portal I/G ratio, as determined both before and after occlusion, is not a reliable measure for the anticipated peripheral I/G ratio, and conversely the two ratios are neither comparable numerically nor are they based upon unidirectional changes of hormones. Therefore, at least in this species, the interpretation of the periph eral I/G ratio as a measure of liver metabo lism should take into account the possibility of divergent splanchnic hormone concentra tions, as well as the modifying influence of the liver on the peripheral blood concentra tions of these hormones.…”

“…In rats, fol lowing an intravenous or oral glucose load, we found almost unchanged glucose toler ance, though at the same time the stimulated insulin release was either reduced (intrave nous glucose) or delayed (oral glucose) as compared with controls [20,27], In dogs, fol lowing segmental pancreatectomy and occlu sion of the residual parenchyma, glucose tol erance is impaired [1]. It seems, therefore, that in addition to species differences, the route of administration of glucose may be crucial in setting the response pattern of blood glucose.…”

“…docrine system [5,18,20,36], The fate of the islet system is uncertain, because duct occlu sion induces atrophy of the exocrine paren chyma [10,11,15,16,24,36], Various inves tigations demonstrate an interrelationship of exocrine and endocrine pancreatic function. For instance, in insulin-dependent diabetes mellitus the exocrine pancreatic function is frequently impaired [7,14,15,16,24,37], and insulin regulates the synthesis of amylase at the level of transcription [31].…”

Ethanol Feeding Aggravates Morphological and Biochemical Parameters in Experimental Chronic Pancreatitis

“…In most animal models of chronic pancreatitis islet preservation is the rule [15, 29]. In a few of those models, diabetes mellitus develops without apparent morphological changes in the islets and with normal pancreatic insulin content [15], suggesting that a dysfunction, rather than destruction, of the islets could be the cause of pancreatic diabetes.…”