The effects of two different cholecystokinin variants, CCK-39 and the carboxyl-terminal octa-peptide CCK-8, on basal and stimulated insulin secretion were studied in the mouse. It was found that both peptides had a dose-dependent stimulating action on insulin secretion with a maximal response of similar magnitude at a dose level of about 5 nmol/kg body weight. This dose induced an increase of plasma concentrations of immunoreactive insulin of about 100 microU/ml. The calculated half-maximal dose was 2.12 nmol/kg for CCK-39 and 3.18 nmol/kg for CCK-8. The insulin-secretory response to CCK-39 and CCK-8 in the absence of other secretagogues was partially abolished by pretreatment with the cholinergic blocker methylatropine as well as with the beta-adrenoceptor blocker L-propranolol. Thus, this great insulin-secretory response to the two peptides seemed to be dependent on intact muscarinic and beta-adrenergic receptors. CCK-39 or CCK-8 administered in a threshold dose prior to half-maximal doses of D-glucose, the cholinergic agonist carbachol, or the beta-adrenergic agonist L-isopropylnoradrenaline (L-IPNA), respectively, displayed different influences on insulin release. CCK-39 potentiated glucose- as well as carbachol-induced insulin secretion, whereas it did not influence L-IPNA-induced insulin release. An equimolar dose of CCK-8, on the contrary, had no apparent effect on either glucose-, carbachol-, or L-IPNA-induced insulin release. This observation indicates that stimulated insulin release is influenced by amino acid sequences other than those of the C-terminal octapeptide in CCK-39 and that the response of the stimulated insulin-secreting cells to CCK-39 is dependent on the nature of the secretagogue.

Animals↗

PubMedDate not supplied

Effects of peptide HI on basal and stimulated insulin and glucagon secretion in the mouse.

Peptide HI (PHI) is a peptide with 27 amino acids that is structurally similar to VIP (vasoactive intestinal peptide). Since PHI, like VIP, has been demonstrated to occur in intrapancreatic neurons, and since VIP earlier was shown to stimulate insulin and glucagon secretion in the mouse, we investigated whether also PHI affects islet hormone secretion in this species. PHI was thereby injected intravenously at dose levels between 0.5 and 8.0 nmol/kg. It was found that PHI did not affect basal levels of insulin of glucagon. However, a slight hyperglycemia was observed after injection of PHI at dose levels above 4.0 nmol/kg. When injected together with glucose (2.8 nmol/kg), PHI (1.0 and 4.0 nmol/kg) potentiated the insulin response by approximately 35% (P less than 0.05) and 50% (P less than 0.01), respectively. In contrast, the insulin response to the cholinergic agonist carbachol (0.16 mumol/kg) or the beta 2-adrenoceptor agonist terbutaline (3.6 mumol/kg) was not affected by PHI. The glucagon response to carbachol was potentiated by PHI (1.0 and 4.0 nmol/kg) by approximately 40% (P less than 0.05) and 55% (P less than 0.01), respectively, whereas the terbutaline-induced increase in plasma glucagon levels was not affected by PHI. In summary, PHI potentiates glucose-induced insulin secretion and carbachol-induced glucagon secretion in the mouse. Since similar effects earlier have been demonstrated for VIP, it is concluded that PHI in this species exerts VIP-like effects.

Animals↗

PubMedDate not supplied

Rye products in the diabetic diet. Postprandial glucose and hormonal responses in non-insulin-dependent diabetic patients as compared to starch availability in vitro and experiments in rats.

Rye flakes, rye bread and white wheat bread were given as suspensions to rats and in standardized breakfast meals to non-insulin-dependent diabetics. In both cases the postprandial glucose response was lower after rye bread than after wheat bread. A larger amount of starch remained in the stomach of the rats 15 min after ingesting rye bread compared to wheat bread, indicating that delayed gastric emptying may be one factor explaining the lower response after rye bread. Although the incremental postprandial glucose areas after rye flakes and wheat bread were similar, the rate of decrease of the glucose curve was slower after flaked rye. This would point to a prolonged absorption of some starch in the rye flakes, also indicated by higher late immunoreactive insulin (IRI) values after that product. In the rats the content of starch in the stomachs 15 min after feeding was higher after rye flakes compared to wheat bread. In vitro incubations with alpha-amylase showed lower availability of the starch in rye flakes than in the breads, indicating that several factors may contribute to the differential postprandial glucose response after the wheat and rye products. The levels of insulin, C-peptide, gastric inhibitory polypeptide (GIP), glucagon, somatostatin, triglyceride and glycerol were followed after the breakfast meals. No pronounced differences of these parameters were seen. However, wheat bread gave significantly higher glucagon and GIP responses than did rye flakes. In conclusion, the absorption pattern and metabolic response after rye bread seems preferable to that after wheat bread. The flaked rye on the other hand was not effective in reducing postprandial glycaemia despite a lower availability of starch in vitro.

Aged↗

PubMedDate not supplied

Increased endocytosis with lysosomal activation in skeletal muscle of dystrophic mouse.

Endocytosis in dystrophic muscles was studied by a combination of biochemical, radiochemical, and light and electron microscopic techniques. It was observed that the uptake of horseradish peroxidase (HRP) and 3H-Inulin in vitro was increased in leg skeletal muscles from dystrophic mice compared with littermate controls. Endocytosis of HRP in vivo was also increased in dystrophic muscles. When HRP was administered intravenously, light microscopic examination of the muscles showed that the macromolecular tracer was present not only in the extracellular space but also as intracellular deposits in several dystropic muscle fibers. Ultrastructural examination of these fibers showed HRP to be present in membrane limited bodies of variable size, some of which likely represented secondary lysosomes, located preferentially close to the A-I junction. HRP was also found inside vacuoles which were sometimes in close vicinity to autophagic vacuoles. Primary uptake vesicles containing HRP appeared to originate from the sarcolemma and the transverse tubules. Biochemical determination of lysosomal enzyme activities revealed elevated levels of both cathepsin D and N-acetylglucosaminidase in dystrophic muscles as compared with controls. The results suggest an increased endocytic activity in dystrophic muscles with distribution of exogenous marcromolecular tracers into endocytic vesicles and lysosomal structures. The hypothesis is put forward that endocytic activity constitutes an important mechanism of lysosomal activation in dystrophic muscles.

Acetylglucosaminidase↗

PubMedDate not supplied

Amine storage and function in peptide hormone-producing cells.

The occurrence of arylethylamines and histamine in normal and neoplastic peptide hormone producing cell types is described. The evidence for their role in hormone formation, storage and release is reviewed.

APUD Cells↗