Jiro Nihei

Effect of endogenous gastric inhibitory polypeptide (GIP) on the removal of triacylglycerol in dogs

In order to clarify the effect of endogenous gastric inhibitory polypeptide (GIP) upon lipid metabolism, the removal of intravenously administered triacylglycerol was investigated following an oral glucose or galactose load in dogs. After an overnight fast, the triacylglycerol emulsion was infused at a constant rate of 1 ml/min for 90 min, and glucose, galactose or tap water was orally administered at 30 min. Blood glucose increased after the glucose load but it did not change following the galactose load or water ingestion. Plasma insulin increased after the glucose load but did not change after galactose or tap water ingestion. Plasma glucagon did not show any discernible change in the three experimental groups. Plasma GIP increased following the glucose or galactose load to 4360 or 1653 pg/ml, respectively. Plasma triacylglycerol increased to the same levels at 30 min in the three experimental groups. The peak levels of plasma triacylglycerol and integrated plasma triacylglycerol for 150 min did not differ in the three groups. Moreover, there was no difference in the removal rate of plasma triacylglycerol following the withdrawal of the fat emulsion. It is concluded from the present study that endogenously released GIP does not elicit any effect upon triacylglycerol removal.

Response of gastric inhibitory polypeptide to fat ingestion in normal dogs

Because of the differences in the data concerning the mechanism by which gastric inhibitory polypeptide (GIP) is secreted following fat ingestion, we were prompted to investigate the characteristics of the GIP response to the triacylglycerol components in normal dogs. Oral administration of glycerol (1 g/kg) slightly elevated the blood glucose levels but not the plasma GIP. Palmitate (1 g/kg) administration did not change the blood glucose whereas the plasma GIP was increased remarkably and remained elevated at 120 min. Oral administration of tricaprylin (2 g/kg) did not elicit any discernible changes in the blood glucose nor in the plasma GIP. Column chromatography of plasma obtained from a dog after palmitate ingestion revealed three GIP-immunoreactive peaks: one peak corresponding to the authentic GIP, one to the large molecular weight peak, and one to the small molecular weight peak. Similar results were obtained with the plasma collected after fat ingestion. From the present study, it would appear that hydrolysis of triacylglycerol plays an important role in GIP release from the intestine. Furthermore, it is concluded that the long chain fatty acids stimulate GIP release whereas the medium chain fatty acids do not.

Effect of glicentin-related peptides on glucagon secretion in anaesthetized dogs.

SummaryRecent studies have demonstrated that glicentin is released during nutrient ingestion. However, the biological function of glicentin remains unclear. In order to clarify the role of glicentin in the enteroinsular axis, the effect of glicentin-related peptides was investigated using in vivo local circulation of canine pancreas. Peaks I and II of gut glucagon-like immunoreactivity, partially purified from porcine intestinal extract by affinity chromatography and gel filtration, synthesized hexadecapeptide of N-terminal glicentin (1–16) and synthesized octapeptide of C-terminal glicentin (62–69) were administered for 10 min into the pancreaticoduodenal artery of canine pancreas. Blood samples were then drawn from the pancreaticoduodenal vein. The administration of peak I of glucagon-like immunoreactivity during arginine infusion in a dosage of 20 ng reduced the glucagon secretion by 42 pmol/1 (p<0.05), whereas peak 11 of glucagon-like immunoreactivity (20 ng) slightly increased the plasma level of insulin, although not significantly. The administration of glicentin (1–16) in a dosage of 400 ng during saline infusion did not alter the plasma insulin level, but reduced the plasma glucagon level in the pancreaticoduodenal vein by 29 pmol/1 (p<0.05). In addition, glicentin [62–691 in a dosage of 400 ng exerted a decrease in both the plasma insulin (40 mU/1,p<0.05) and glucagon level (27 pmol/l,p<0.05). The present study demonstrates the suppression of pancreatic glucagon release during the infusion of peak I glucagon-like immunoreactivity and N- or C-terminal glicentin-related peptide. Therefore, it is suggested that glicentin released during nutrient intake might inhibit the secretion of glucagon.

Response of gastric inhibitory polypeptide (GIP) to oral administration of nutrients in normal and pancreatectomized dogs.

In order to clarify the response of plasma gastric inhibitory polypeptide (GIP) to various nutrients and to investigate the relationship between the pancreas and GIP secretion, an experimental study was performed using normal and pancreatectomized dogs. Oral administration of glucose (2 g/kg) or butter (2 g/kg) resulted in an increase of plasma GIP in five normal dogs. In contrast, oral administration of arginine (1 g/kg) did not produce any discernible changes in plasma GIP in normal dogs. In a group of nine pancreatectomized dogs, the fasting level of plasma GIP did not differ from that of the control group. Furthermore, glucose ingestion in the pancreatectomized group resulted in the same pattern and the same degree of change in plasma GIP as it did in the normal controls. In contrast, plasma GIP did not change at all following fat loading in the pancreatectomized group. However, butter with pancreatic enzymes elicited a significant rise of plasma GIP in the pancreatectomized dogs. The present study indicates that plasma GIP increases following oral administration of glucose or fat but not arginine. Furthermore, it is demonstrated that GIP secretion following fat ingestion occurs only after fat digestion by pancreatic enzymes. In addition, the findings observed in the present study do not support the existence of feedback effect of insulin on GIP secretion.

Effect of intraluminal administration of amino acids upon plasma glicentin

To see what effect intraluminal amino acids would have on glicentin secretion, we put a mixture of 10 amino acids (1 g/kg) into the duodenum of five normal, conscious piglets. Their plasma nitrogen rose, as did insulin and glucagon measured with C-terminal-specific antiserum. Plasma total immunoreactive glucagon, determined with non-specific antiserum, rose from 2753 +/- 460 pg/ml to a peak of 4434 +/- 1352 pg/ml at 30 min. Plasma glicentin, determined with R 64 antiserum, rose from a fasting level of 297 +/- 70 pmol/l to a peak of 702 +/- 167 pmol/l at 45 min. We also gave oral arginine to 6 pancreatectomized dogs to investigate why the plasma glicentin rises after amino acid ingestion. Arginine raised the plasma total immunoreactive glucagon from 1120 +/- 214 pg/ml to a peak of 2266 +/- 512 pg/ml at 45 min. We conclude that intraluminally administered amino acids enhance glicentin secretion from the gut.

Measurement of Glucagon in Human Plasma by Enzyme Immunoassay

In order to investigate the validity of an enzyme immunoassay for glucagon, the glucagon levels of human plasma were determined by both enzyme immunoassay (EIA) and radioimmunoassay (RIA). After a glucose load, plasma glucagon measured by both EIA and RIA fell in 12 normal subjects. The glucagon levels measured by both assays during glucose tolerance test showed good agreement in a group of 10 patients. After arginine infusion, plasma glucagon increased in 6 normal subjects and 3 patients and glucagon values measured by EIA correlated well with those by RIA. The present study demonstrates correlation between glucagon levels measured by RIA and EIA and indicates the usefulness of EIA for determining glucagon in human plasma.

Effect of a new lente insulin on diabetics

Thirty diabetics who had been receiving ordinary insulin were switched to S-lente insulin, a new mixture of four parts semilente and six parts ultralente insulin. Eight times a day, we measured the glucose, insulin, and C-peptide (CPR) in their blood. Those with more than 250 mg/dl postprandial glucose were designated group A (18 patients) and the other were designated group B (12 patients). Group A diabetics experienced a significant decrease in fasting blood glucose levels whereas group B did not. S-lente improved the daily blood glucose profiles of 72% of group A and 25% of group B. It slightly reduced the sum of the daily blood glucose in group A and did not affect those of group B. The M-value fell significantly in group A but not in group B. Changes in this value correlated significantly with those of blood glucose determination sums. The sums of the determinations of free plasma insulin and CPR remained unaffected by the new insulin. It is concluded that S-lente insulin controls the blood glucose of diabetics whose postprandial blood glucose cannot be controlled by ordinary insulin.

Factors influencing the development of diabetic vascular complications.

In order to elucidate the factors influencing the development of diabetic vascular complications, a retrospective clinical study was carried out in 255 patients, who had been treated in our diabetes clinic for more than 10 years. The patients were divided into three groups according to their retinal lesions: group A, 89, had no retinal lesions; group B, 118, Scott I and II; and group C, 48, Scott III or more advanced lesions. Although there were no significant differences in body weight or age at onset of diabetes between the three groups, the severity of the disease at the first visit and the method of treatment were regarded as important factors in the development of vascular complications. Hypertension, albuminuria and hypercholesterolemia were observed more often in group C than groups A and B, while there was no difference in EKG abnormalities between the three groups. No significant difference was demonstrated concerning control of blood glucose, incidence of hypoglycemia, urinary glucose and ketone bodies, serum triglyceride, hemoglobin A1c, beta-N-acetylglucosaminidase or serum lipoperoxide. These results suggest that the complicated mechanism involved in the development of vascular complications should be investigated and a long-term dynamic observation should be carried out.