Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis

Abstract

Chronic pancreatitis (CP) is a continuing or relapsing inflammatory disease of the pancreas. In approximately one-third of all cases, no aetiological factor can be found, and these patients are classified as having idiopathic disease. Pathophysiologically, autodigestion and inflammation may be caused by either increased proteolytic activity or decreased protease inhibition. Several studies have demonstrated mutations in the cationic trypsinogen gene (PRSS1) in patients with hereditary or idiopathic CP. It is thought that these mutations result in increased trypsin activity within the pancreatic parenchyma. Most patients with idiopathic or hereditary CP, however, do not have mutations in PRSS1 (ref. 4). Here we analysed 96 unrelated children and adolescents with CP for mutations in the gene encoding the serine protease inhibitor, Kazal type 1 (SPINK1), a pancreatic trypsin inhibitor. We found mutations in 23% of the patients. In 18 patients, 6 of whom were homozygous, we detected a missense mutation of codon 34 (N34S). We also found four other sequence variants. Our results indicate that mutations in SPINK1 are associated with chronic pancreatitis.

The diabetes prone BB rat model of IDDM shows duration of breastfeeding to influence Type 1 diabetes development later in life

“…To the Editor: The diabetogenic agents, streptozotocin and alloxan induce insulin deficiency due to their selective pancreatic beta-cell toxicity [1]. However, there are significant species differences in the diabetogenicity of streptozotocin and alloxan [1].…”

“…Our data show that diabetes development in diabetes-prone (DP)-BB rats can be delayed and prevented by prolonging the nursing period of these rats. These results provide experimental evidence strengthening human epidemiological data that the duration of exclusive breastfeeding influences diabetes development later in life.Most human epidemiological data suggest that a short, as opposed to a long, duration of exclusive breastfeeding is related with an increased risk for IDDM development [1,2,3,4,5]. The introduction of cow's milk and wheat proteins at a young age has been suggested as potential diabetogenic risk factors for infants at risk of developing diabetes [1,2,3,4,5].…”

“…The introduction of cow's milk and wheat proteins at a young age has been suggested as potential diabetogenic risk factors for infants at risk of developing diabetes [1,2,3,4,5]. The importance of food ingredients in IDDM is further illustrated by the fact that the development of diabetes is reduced in DP-BB rats receiving a special diet in which hydrolysed casein is the sole source of protein [6].…”

“…The importance of food ingredients in IDDM is further illustrated by the fact that the development of diabetes is reduced in DP-BB rats receiving a special diet in which hydrolysed casein is the sole source of protein [6]. Since, in epidemiological studies the period of nursing is established using questionnaires, the exact duration of breastfeeding remains unclear and duration of breastfeeding varies considerably between the siblings [1,2,3,4,5]. DP-BB rats normally spontaneously develop diabetes between 60 and 160 days of age and are used as an animal model for the study of Type 1 diabetes.…”

“…Such experiments will provide additional experimental evidence in contribution to epidemiological data [1,2,3,4,5] on this intriguing topic. (a) Diabetes prone BB rats received exclusively mother's milk and were weaned at 21 days (■ ■; n=25), 31 days (• •; n=12) or 40 days (▲ ▲; n=11).…”