SGLT2 Inhibitors Suppress Alpha-Adrenergic Tone and Morning Elevation of Plasma Glucose Levels

Background and objective: The effects of hypothyroidism during pregnancy and lactation on carbohydrate metabolism have been mostly studied in male animals. The aim of this study is therefore to investigate effect of fetal and neonatal hypothyroidism (FH and NH) on the glucose tolerance in middle-aged female rat offspring. Methods: Pregnant female rats were divided into three groups: Rats in the control group consumed tap water, while those in the FH and NH groups consumed 250 mg/L of 6-propyl-2-thiouracil (PTU) in their drinking water during gestation or lactation periods, respectively. After weaning, the female offspring were separated and divided into 3 groups (n=8/group): Control, FH, and NH. Body weight was recorded monthly and intravenous glucose tolerance test (IVGTT) was performed at month 12. Results: Compared to controls, female rats in the FH group had significantly higher plasma glucose levels than controls throughout the IVGTT except at min 60. Values at min 5 of the FH and control group were 196.1±1.9 and 155.3±5.9 mg/dL, respectively (P<0.05). In the NH group, plasma glucose levels were significantly higher only at min 5 (185.7±14.1 vs. 155.3±5.9 mg/dL, P<0.05). Conclusion: Hypothyroidism during fetal or neonatal periods caused glucose intolerance in middle-aged female offspring rats.

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Prevention of Postprandial Hyperglycemia by Ophthalmic Nanoparticles Based on Protamine Zinc Insulin in the Rabbit

Pharmaceutics ◽

10.3390/pharmaceutics13030375 ◽

2021 ◽

Vol 13 (3) ◽

pp. 375

Author(s):

Saori Deguchi ◽

Fumihiko Ogata ◽

Takumi Isaka ◽

Hiroko Otake ◽

Yosuke Nakazawa ◽

...

Keyword(s):

Blood Glucose ◽

Plasma Glucose ◽

Polyacrylic Acid ◽

Rabbit Model ◽

Postprandial Hyperglycemia ◽

Postprandial Blood Glucose ◽

Oral Glucose ◽

Glucose Levels ◽

Protamine Zinc Insulin ◽

Bead Mill

Postprandial hyperglycemia, a so-called blood glucose spike, is associated with enhanced risks of diabetes mellitus (DM) and its complications. In this study, we attempted to design nanoparticles (NPs) of protamine zinc insulin (PZI) by the bead mill method, and prepare ophthalmic formulations based on the PZI-NPs with (nPZI/P) or without polyacrylic acid (nPZI). In addition, we investigated whether the instillation of the newly developed nPZI and nPZI/P can prevent postprandial hyperglycemia in a rabbit model involving the oral glucose tolerance test (OGTT). The particle size of PZI was decreased by the bead mill to a range for both nPZI and nPZI/P of 80–550 nm with no observable aggregation for 6 d. Neither nPZI nor nPZI/P caused any noticeable corneal toxicity. The plasma INS levels in rabbits instilled with nPZI were significantly higher than in rabbits instilled with INS suspensions (commercially available formulations, CA-INS), and the plasma INS levels were further enhanced with the amount of polyacrylic acid in the nPZI/P. In addition, the rapid rise in plasma glucose levels in OGTT-treated rabbits was prevented by a single instillation of nPZI/P, which was significantly more effective at attenuating postprandial hyperglycemia (blood glucose spike) in comparison with nPZI. In conclusion, we designed nPZI/P, and show that a single instillation before OGTT attenuates the rapid enhancement of plasma glucose levels. These findings suggest a better management strategy for the postprandial blood glucose spike, which is an important target of DM therapy.

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SGLT2 inhibitors: a narrative review of efficacy and safety

Journal of Osteopathic Medicine ◽

10.1515/jom-2020-0153 ◽

2021 ◽

Vol 121 (2) ◽

pp. 229-239

Author(s):

Donald S. Nelinson ◽

Jose M. Sosa ◽

Robert J. Chilton

Keyword(s):

Adverse Events ◽

Sglt2 Inhibitor ◽

Sglt2 Inhibitors ◽

Narrative Review ◽

Atherosclerotic Cardiovascular Disease ◽

Comorbid Conditions ◽

Postprandial Plasma Glucose ◽

Renal Outcomes ◽

Glucose Levels ◽

Wide Range

Abstract Type 2 diabetes mellitus (T2DM) is a cardio-renal-metabolic condition that is frequently associated with multiple comorbidities, including atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and chronic kidney disease (CKD). The sodium-glucose co-transporter-2 (SGLT2) inhibitors, which lower glycated hemoglobin, fasting and postprandial plasma glucose levels, body weight, and blood pressure, as well as reduce the risk of a range of cardiovascular and renal outcomes without increasing hypoglycaemic risk, have heralded a paradigm shift in the management of T2DM. These drugs are compatible with most other glucose-lowering agents and can be used in patients with a wide range of comorbid conditions, including ASCVD, HF, and CKD, and in those with estimated glomerular filtration rates as low as 30 mL/min/1.73 m2. However, there are misunderstandings surrounding the clinical implications of SGLT2 inhibitors’ mechanism of action and concerns about the key adverse events with which this class of drugs has been associated. This narrative review summarizes the data that support the efficacy of SGLT2 inhibitors in reducing the risks of cardiovascular and renal outcomes in patients with T2DM and comorbid conditions and clarifies information relating to SGLT2 inhibitor-related adverse events.

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Assessment of factors that determine the mean absolute relative difference in flash glucose monitoring with reference to plasma glucose levels in Japanese subjects without diabetes

Endocrine Journal ◽

10.1507/endocrj.ej19-0488 ◽

2020 ◽

Vol 67 (5) ◽

pp. 537-544 ◽

Cited By ~ 1

Author(s):

Satoshi Yoshino ◽

Eijiro Yamada ◽

Shuichi Okada ◽

Yasuyo Nakajima ◽

Ryo Shibusawa ◽

...

Keyword(s):

Plasma Glucose ◽

Glucose Monitoring ◽

Relative Difference ◽

Flash Glucose Monitoring ◽

Glucose Levels ◽

The Mean ◽

Japanese Subjects

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Body Mass Index, Fasting Plasma Glucose Levels, and C-peptide Levels as Predictors of the Future Insulin Use in Japanese Type 2 Diabetic Patients

Endocrine Journal ◽

10.1507/endocrj.k09e-279 ◽

2010 ◽

Vol 57 (3) ◽

pp. 237-244 ◽

Cited By ~ 27

Author(s):

Atsushi GOTO ◽

Maki TAKAICHI ◽

Miyako KISHIMOTO ◽

Yoshihiko TAKAHASHI ◽

Hiroshi KAJIO ◽

...

Keyword(s):

Body Mass Index ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Diabetic Patients ◽

Type 2 Diabetic Patients ◽

C Peptide ◽

Glucose Levels ◽

Insulin Use ◽

Type 2 Diabetic

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Examination of Potential Mechanisms in the Enhancement of Cerebral Blood Flow by Hypoglycemia and Pharmacological Doses of Deoxyglucose

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-199701000-00008 ◽

1997 ◽

Vol 17 (1) ◽

pp. 54-63 ◽

Cited By ~ 25

Author(s):

Naoaki Horinaka ◽

Nicole Artz ◽

Jane Jehle ◽

Shinichi Takahashi ◽

Charles Kennedy ◽

...

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Glucose Metabolism ◽

Plasma Glucose ◽

Plasma Lactate ◽

Insulin Hypoglycemia ◽

Glucose Levels ◽

Arterial Blood ◽

Arterial Plasma

Cerebral blood flow (CBF) rises when the glucose supply to the brain is limited by hypoglycemia or glucose metabolism is inhibited by pharmacological doses of 2-deoxyglucose (DG). The present studies in unanesthetized rats with insulin-induced hypoglycemia show that the increases in CBF, measured with the [14C]iodoantipyrine method, are relatively small until arterial plasma glucose levels fall to 2.5 to 3.0 m M, at which point CBF rises sharply. A direct effect of insulin on CBF was excluded; insulin administered under euglycemic conditions maintained by glucose injections had no effects on CBF. Insulin administration raised plasma lactate levels and decreased plasma K+ and HCO3– concentrations and arterial pH. These could not, however, be related to the increased CBF because insulin under euglycemic conditions had similar effects without affecting CBF; furthermore, the inhibition of brain glucose metabolism with pharmacological doses (200 mg/kg intravenously) of DG increased CBF, just like insulin hypoglycemia, without altering plasma lactate and K+ levels and arterial blood gas tensions and pH. Nitric oxide also does not appear to mediate the increases in CBF. Chronic blockade of nitric oxide synthase activity by twice daily i.p. injections of NG-nitro-L-arginine methyl ester for 4 days or acutely by a single i.v. injection raised arterial blood pressure and lowered CBF in normoglycemic, hypoglycemic, and DG-treated rats but did not significantly reduce the increases in CBF due to insulin-induced hypoglycemia (arterial plasma glucose levels, 2.5-3 m M) or pharmacological doses of deoxyglucose.

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Plasma glucose levels and outcome after aneurysmal subarachnoid hemorrhage

Journal of Neurosurgery ◽

10.3171/jns.1993.79.6.0885 ◽

1993 ◽

Vol 79 (6) ◽

pp. 885-891 ◽

Cited By ~ 87

Author(s):

Giuseppe Lanzino ◽

Neal F. Kassell ◽

Teresa Germanson ◽

Laura Truskowski ◽

Wayne Alves

Keyword(s):

Subarachnoid Hemorrhage ◽

Plasma Glucose ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Ct Scans ◽

Good Recovery ◽

Glucose Levels ◽

Poor Outcome ◽

Elevated Glucose ◽

Mean Glucose

✓ Plasma glucose levels were studied in 616 patients admitted within 72 hours after subarachnoid hemorrhage (SAH). Glucose levels measured at admission showed a statistically significant association with Glasgow Coma Scale scores, Botterell grade, deposition of blood on computerized tomography (CT) scans, and level of consciousness at admission. Elevated glucose levels at admission predicted poor outcome. A good recovery, as assessed by the Glasgow Outcome Scale at 3 months, occurred in 70.2% of patients with normal glucose levels (≤ 120 mg/dl) and in 53.7% of patients with hyperglycemia (> 120 mg/dl) (p = 0.002). The death rates for these two groups were 6.7% and 19.9%, respectively (p = 0.001). The association was still maintained after adjusting for age (> or ≤ 50 years) and thickness of clot on CT scans (thin or thick) in the subset of patients who were alert/drowsy at admission. Increased mean glucose levels between Days 3 and 7 also predicted a worse outcome; good recovery was observed in 132 (73.7%) of 179 patients who had normal mean glucose levels (≤ 120 mg/dl) and 160 (49.7%) of 322 who had elevated mean glucose levels (> 120 mg/dl) (p < 0.0001). Death occurred in 6.7% and 20.8% of the two groups, respectively (p < 0.0001). It is concluded that admission plasma glucose levels can serve as an objective prognostic indicator after SAH. Elevated glucose levels during the 1st week after SAH also predict a poor outcome. However, a causal link between hyperglycemia and outcome after delayed cerebral ischemia, although suggested by experimental data, cannot be established on the basis of this study.

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