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A 7-year-old girl with severe hereditary pancreatitis underwent total pancreatectomy. A total of 160 000 islet equivalents (6400 islet/kg) were transplanted to the brachioradialis muscle of the right forearm. Her plasma C-peptide level was undetectable after pancreatectomy but increased to 1.37 ng/mL after 17 days; at this time point, her insulin requirement was 0.75 units of insulin/kg/day. At 5-and 27-months, her hemoglobin A1c (HbA1c) and insulin requirements were 4.5 and 5.3% and 0.3 and 0.18 units/kg/day, respectively. Basal and stimulated C-peptide levels were 0.67 ± 0.07 and 3.36 ± 1.37 ng/mL, respectively. Stimulated insulin levels were 30% higher in the islet-bearing arm compared to the contralateral arm after glucagon stimulation. After surgery and islet transplantation, the quality of life improved dramatically and she gained 8 kg of weight. In summary, a normal HbA1c, a low insulin requirement and the absence of recurrent hypoglycemia and the gradient of insulin between the arms indicate that the intramuscularly transplanted islets contribute to a long-term clinically significant metabolic control.

The effect of conjugated bile salts on the actirity of pancreatic lipase depends on their concentration in relation to their critical miceIlar concentration.Below the critical micellar concentration, conjugated bile salts slightly stimulate the initial rate of hydrolysis of tributyrine, an effect that may be caused by a protection of the enzyme from inactivation at the substrate-water interface.Above the critical micellar concentration, conjugated bile salts almost completely inhibit lipase. The inhibition is more marked in alkaline reactions resulting in a pH optimum shift with increasing bile salt concentration. Bile salt inhibition of lipase is related both to the concentration of bile salt and to the substrate concentration or rather to substrate surface area, and most probably is complete when the interface is saturated with detergent. Co-lipase, in the absence of bile salts, stimulates the activity of lipase, 1.3 to 1.4-fold in the whole pH range of its achivity. Co-lipase overcomes the inhibition of lipase caused by bile salts with a shift in the pH optimum to 6-7 compared to 8-9 for lipase alone.The different conjugated bile salts have similar effects, consideration being taken to differences in their critical micellar concentration; free bile salts have a less inhibitory effect on lipase and the stimulation by co-lipase shows no pH optimum shift.Detergents of the acyltaurine type such as decanoyltaurine and dodecanoylsarcosyltaurine inhibit lipase in a similar manner to the conjugated bile salts and this inhibition is also released by co-lipase. Detergents such as dodecylsulphate above the micellar concentration, irreversibly inhibit lipase. The simultaneous presence of bile salts protects the enzyme from being irreversibly inactivated.Lipase and co-lipase interact in a stoichiometrical relationship and it appears justified to classify co-lipase as a co-enzyme for lipase.Studies of the effect of bile salt and other detergents on the activity of pancreatic lipase in the past, have given results difficult to interpret and which many times are conflicting. Several reasons for this are obvious. Lipase functions in the interface of water-insoluble substrates, which, to properly disperse in water, have been added with a detergent and/or some other kind of surface-active agent which by itself can be supposed to interact with the reaction. The concentration of the detergent has in general not been related to its critical micellar concentration and furthermore for lipase, in general even the most highly purified preparations have been contaminated to a varying extent by a protein co-factor named co-lipase that has recently been shown to interact with lipase and lipase detergent systems [1,2]. Pancreatic lipase when prepared essentially free of co-lipase, is strongly inhibited by conjugated bile salts at or above their critical micellar concentration.Addition of co-lipase restores activity to the bilesalt-inhibited lipase and gel-filtration experiments indicate that co-lipase in bile salt solution makes a dimer w...

The phase behavior of monoglyceride/water systems, with oleic and linoleic acid as the dominating fatty acid residues, was investigated. Increased solubilization of triglycerides (oil) or oleic acid in the cubic liquid-crystalline phase formed by monoglyceride and water resulted in the formation of a reversed hexagonal liquid-crystalline phase followed by an L2-phase. The liquid-crystalline phases have different dispersion properties compared to each other in dilute micellar bile salt solutions. The cubic phase is found to be easily dispersed. The relevance of aqueous lipid phases other than micellar is discussed in relation to intestinal lipid digestion and absorption.

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