Diabetic control after total pancreatectomy

Abstract

Historically, Rockey [1] demonstrated the feasibility of total pancreatectomy on a patient with pancreatic carcinoma in 1943 even if at autopsy, 1 g of pancreatic tissue adjacent to the duodenum was found. Thus, the procedure performed by Priestley et al. [2] in 1944 was considered as the first true total pancreatectomy. For many years, the use of total pancreatectomy was limited in surgical practice, but in the last 25 years, thanks to highly sensitive imaging techniques, the operability of many pancreatic diseases has increased and pancreatic resection has become more common as the operative mortality risk has fallen to less than 2%. Removal of the pancreas is often associated with a glucose intolerance called ‘pancreatogenic diabetes’; most of the studies in this field have emphasised the difficulties in glucose conanalysed after discontinuing insulin infusion, and the plasma clearance rate of insulin is significantly higher in patients with pancreatogenic diabetes than in those with type I diabetes. Thus, an up-regulation of peripheral insulin receptors in response to insulin deficiency occurs, rendering these patients uniquely sensitive to hormone replacement. Glucose intolerance after pancreatectomy may not be due to insulin deficiency alone; the reduction in beta-cell mass after an 80% proximal pancreatectomy in dogs resulted in lower peripheral insulin levels and altered glucose disappearance after glucose challenge [9]. In the altered glucose metabolism of pancreatectomised subjects, an important role is also played by glucagon deficiency [10]. After total pancreatectomy in ducks, glucagon levels are trol, considering the apancreatic patients as ‘brittle diabetics’ [3–5]. The metabolic control of apancreatic patients is rather complex because the pancreas secretes most of the hormones involved in glycaemic homeokinesis such as insulin, glucagon and pancreatic polypeptide (PP); furthermore, other gut hormones are involved in this control. The insulinsecreting beta cells are distributed evenly throughout the pancreas, whereas glucagon cells and PP cells are localised reduced to 45% of the preoperative level immediately following the procedure [11]. Controversy persists, however, over whether total pancreatectomy removes all sources of glucagon production. Some authors have reported no detectable circulating plasma immunoreactive glucagon after total pancreatectomy in humans [10], whereas others have detected varying amounts of the hormone in the plasma of pancreatectomised patients [12]. Although there may be enteric sources of glucagon production in humans after total selectively in the tail and the head of the pancreas, respectively. Insulin stimulates the transport of ions, glucose and pancreatectomy, there is a profound glucagon deficiency that, in combination with insulin deficiency, can produce a metabolic crisis. It has been reported that the metabolic r t [ m t i i p i c a o r h m t c h esponse to glucagon was considerably more pronounced in otal pancreatectomy patients than in type I diabetic patients 13]. Therefore, a state of chronic glucagon deficiency may odify the effect of glucagon on the liver, presumably hrough up-regulation of glucagon receptors which results n enhanced hyperglycaemic responsiveness. Despite an ncrease in peripheral insulin receptor availability, however, ancreatogenic diabetes is also accompanied by a decrease n hepatic insulin receptor availability [14]. This paradoxial effect is probably due to a concurrent deficiency in PPs nd renders the liver resistant to the suppressant effects f insulin on hepatic glucose production. In fact, a critical ole for PP as a hormonal mediator of glucose metabolism as been suggested. This hormone is released in a biphasic anner in response to feeding and it has been shown o inhibit exocrine pancreatic secretion and gallbladder ontraction. PP receptors have also been identified on rat epatocyte plasma membranes [15]. Studies on a canine amino acids across cell membranes, has anabolic effects such as protein synthesis and lipogenesis, and has growthpromoting effects secondary to the stimulation of RNA and DNA synthesis [6]. Insulin is known to be a potent inhibitor of glucose production in the liver in humans and, under euglycaemic conditions, the intravenous infusion of insulin causes hepatic glucose production to decrease rapidly. The release of insulin into the portal vein after a glucose load causes suppression of net hepatic glucose production, stimulation of net hepatic glucose uptake and glycogen synthesis [7]. Comparing the insulin action of patients with pancreatogenic diabetes to those with type I diabetics [8], enhanced extrahepatic tissue sensitivity to physiologic hyperinsulinaemia and higher insulin binding to red blood cell receptors have been observed in patients with pancreatogenic diabetes. Insulin decay has also been