Highly variable gastric emptying in patients with insulin dependent diabetes mellitus.

Some diabetic patients--particularly those with nausea and vomiting--frequently have evidence of delayed gastric emptying while other diabetic patients may in fact exhibit accelerated gastric emptying. Whether the presence or absence of symptoms of upper gastrointestinal dysfunction correlated with objective measures of gastric emptying in insulin dependent diabetic subjects was investigated. Twenty one insulin dependent diabetic patients underwent a solid phase gastric emptying scintiscan using in vivo labelled chicken liver. Thirteen patients had symptoms suggestive of gastrointestinal dysfunction (nausea, vomiting, early satiety, or constipation), while eight patients had no gastrointestinal symptoms. Eleven patients had orthostatic hypotension. All patients had been diabetic since childhood or adolescence. As a group, the diabetic patients showed a half time (T50) of gastric emptying (mean (SD) 150.0 min (163.7) that was not significantly different from that of 12 healthy control subjects (148.1 min (62.4)). Those diabetic patients without gastrointestinal symptoms and without orthostatic hypotension, however, showed a gastric emptying half time (70.1 min (41.6)) that was significantly faster than that of the control subjects. Conversely, those diabetic patients with nausea, vomiting, and early satiety (or early satiety alone) showed T50 values that were significantly greater than those of the diabetic patients without these symptoms. No correlation was found between the T50 value and the duration of diabetes, the fasting blood glucose at the time of study, or the respiratory variation in heart rate (E:I ratio). These observations indicate that highly variable rates of gastric emptying occur in insulin dependent diabetic patients, and that accelerated gastric emptying may occur in diabetic patients who have no symptoms of gastrointestinal dysfunction.

Effect of streptozotocin-induced diabetes mellitus on release of vasoactive intestinal polypeptide from rodent small intestine.

Representative longitudinal muscle strips (6 x 10 mm) from proximal and distal small intestine were excised from control and streptozotocin-treated rats after one month of untreated and insulin-treated diabetes. Untreated diabetes significantly reduced tissue concentrations of vasoactive intestinal polypeptide (VIP) at both intestinal loci. Insulin treatment of the diabetic animals restored tissue VIP concentrations to control group levels, although the beneficial effect of insulin treatment was only significant in the duodenum. Spontaneous release of VIP was significantly attenuated by untreated diabetes at both intestinal sites. In the duodenum, insulin treatment of the diabetic animals restored VIP release to levels indistinguishable from control group values. In the ileum, insulin treatment produced levels of VIP release that were not significantly different from those of the control and untreated diabetic groups. Tetrodotoxin (5 x 10(-6) M) significantly--but incompletely--inhibited VIP release from control group animals at both intestinal sites. These observations indicate that diabetes mellitus significantly diminishes VIP tissue concentrations and release from intestinal myenteric nerves. These abnormalities improve with insulin treatment. However, the mechanisms of VIP release from proximal and distal intestine appear to differ not only in their response to the diabetic state, but also in their response to insulin treatment.

Impaired rodent vagal nerve sodium-potassium-ATPase activity in streptozotocin diabetes.

Experimental diabetes in rodents is associated with diminished activity of sodium-potassium-adenosine triphosphatase (Na+ -K+ -ATPase) in the sciatic nerve, an abnormality that has been invoked as being factorial in the genesis of diabetic peripheral neuropathy. Whether a parallel metabolic abnormality occurs in the autonomic vagus nerve is unknown. To answer this question, adult male rats made diabetic with streptozotocin (45 mg/kg) and age-matched nondiabetic controls were killed at 1 and 3 months after induction of diabetes. The cervical vagi and sciatic nerves were excised, weighed, and homogenized, and Na+ -K+ -ATPase activities were determined. After 1 month, the diabetic animals showed a significantly reduced sciatic nerve Na+ -K+ -ATPase activity as compared with respective controls, whether expressed in micromoles per gram wet weight per hour (20.5 +/- 4.9 [mean +/- SEM] vs 61.6 +/- 13.0) or micromoles per milligram of protein per hour (0.77 +/- 0.21 vs 2.48 +/- 0.57, p < 0.05, diabetic vs control, respectively). Diabetic vagus nerve Na+ -K+ -ATPase activity was also diminished (40.6 +/- 6.9 mumol/gm wet weight per hour vs 63.2 +/- 9.7 mumol/gm wet weight per hour and 3.83 +/- 0.81 mumol/mg protein per hour vs 5.86 +/- 0.73 mumol/mg protein per hour), but the results did not reach statistical significance. After 3 months, diabetic sciatic nerve Na+ -K+ -ATPase activity was still significantly less than the control group value (16.89 +/- 3.91 mumol/mg wet weight per hour vs 38.9 +/- 4.24 mumol/gm wet weight per hour and 0.48 +/- 0.11 mumol/mg protein per hour vs 1.04 +/- 0.14 mumol/mg protein per hour; p < 0.05, diabetic vs control, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Accelerated gastric emptying in diabetic rodents: effect of insulin treatment and pancreas transplantation.

Gastric emptying of a suspended solid, digestible meal was examined after 30 to 90 days of diabetes in two strains of streptozotocin-treated rodents and in genetically diabetic BB/Wor rats. After a 14-hour overnight fast the animals were gavage-fed 1.0 gm of rat food suspended in water and were killed 30 minutes later. Ligatures were placed around the lower esophageal sphincter and the pylorus and the stomachs were removed intact. The stomachs were evacuated and the gastric contents and gastric remnant were separately dried and weighted. Both the streptozotocin-treated and BB/Wor rats showed significantly accelerated (1.5- to 2.2-fold) rates of gastric emptying of the meal compared with respective nondiabetic control animals. Streptozotocin-treated diabetic animals that received daily insulin supplementation or those that had undergone pancreas transplantation shortly after induction of diabetes showed a similar reduction in blood glucose levels and normal rates of gastric emptying. Diabetes had a significant but variable effect on gastric mass and body weight. This response was dependent on the strain of animal examined, whether or not insulin supplementation was administered, or whether the animal underwent pancreas transplantation. These observations indicate that early diabetes in rodents has a prokinetic effect on gastric emptying of a suspended solid digestible meal. Restoration of euglycemia by insulin treatment or pancreas transplantation is associated with return of the gastric emptying rate to normal. These changes in gastric emptying appear to be independent of the effects of diabetes on gastric mass.

Structural and functional characteristics of muscle from diabetic rodent small intestine.

After 30 days of streptozotocin-induced diabetes, the small intestine from untreated diabetic, insulin-treated diabetic, and nondiabetic rodents was excised in toto and measured. Despite a net loss in body weight, the diabetic animals showed a near twofold increase in small intestinal weight. This was characterized by a 148% increase in mucosal mass as well as a 39% increase in intestinal smooth muscle mass (P less than 0.05, respectively). The diabetic intestine was significantly longer and had a greater diameter and surface area. Diabetes significantly increased mucosal mass per unit surface area but produced an insignificant decrease in smooth muscle mass per unit surface area. Insulin treatment of the diabetic animals prevented the increase in total mucosal mass and mucosal mass per unit surface area. Insulin treatment also prevented the increase in smooth muscle mass, but reduced smooth muscle mass per unit surface area to a level significantly less than that found in nondiabetic intestine. In vitro dose-response studies of circular and longitudinal small intestinal muscle from the diabetic animals showed normal tension development and sensitivity to both bethanechol chloride and physostigmine. These observations show that the diabetic state produces alterations in not only mucosal but also smooth muscle mass in the small intestine. However, despite these morphological changes, diabetic intestinal smooth muscle retains its sensitivity to cholinergic stimulation and its capacity for tension generation.